AIM:To explore a novel mechanism for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), upregulation of CD4+ and CD8+T lymphocytes participating in the patho-physiological process of chronic hepatitis B ...AIM:To explore a novel mechanism for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), upregulation of CD4+ and CD8+T lymphocytes participating in the patho-physiological process of chronic hepatitis B (CHB). METHODS: The levels of serum soluble TRAIL (sTRAIL), serum IFN-γ and membrane-bound TRAIL expression on peripheral leucocytes from 58 CHB patients were examined by ELISA and flow cytometry respectively. The levels of TRAIL were compared with the baseline levels of 17 healthy controls, and correlation analysis was performed between ALT, TBIL, PT, morphological change in hepatic tissues, and serum IFN-γ. RESULTS: The results showed that TRAIL levels on membranes of CD4+, CD8+ T cells in CHB patients were much higher than those in healthy controls (P<0.001), and were correlated with serum TBIL (r=0.354, P= 0.008 for CD4+ and r= 0.522, P= 0.000 for CD8+, respectively), ALT (r= 0.393, P= 0.003 for CD8+), PT (r = 0.385, P = 0.004 for CD8+) and serum IFN-y level (r = 0.302, P= 0.011 for CD4+ and r= 0.307, P= 0.009 for CD8+). On the contrary to membrane-bound TRAIL expression, serum level of sTRAIL was not correlated with that of TBIL and PT, though it was higher than that of the normal population and was positively correlated with serum HBeAg expression (r= 0.695, P = 0.001). CONCLUSION: The expression level of TRAIL on the membrane of lymphocytes was upregulated and associated with the liver injury in CHB patients. These findings suggest that upregulation of TRAIL expression may be induced by virus antigen and inflammatory cytokine IFN-γ.展开更多
The function of CD4+CD25+ regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided int...The function of CD4+CD25+ regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-β1 and IFN-γ) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P〈0.01), the inhibitory ability of Treg on the T lymphocytes proliferation was reduced (P〈0.01), IFN-γ levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-γ was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.展开更多
BACKGROUND: Methylprednisolone (MP) can affect the survival of CD4(+) T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown th...BACKGROUND: Methylprednisolone (MP) can affect the survival of CD4(+) T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown that toll-like receptors (TLRs) on CD4(+) T cells can directly modulate adaptive immune responses by affecting the survival and proliferation of activated CD4(+) T cells. This study aimed to investigate the relationship between MP, TLRs and activated CD4(+) T cells. METHODS: We separated and purified CD4(+) T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1). We then assessed CD4(+) T cell survival and proliferation and the expression of NF-kappa B and AP-1. RESULTS: Activated CD4(+) T cells showed increased TLR-3 and TLR-9 mRNA expression, but polyinosinic-polycytidylic acid (poly I:C) and MP had no effect on the expression of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased the survival of activated CD4(+) T cells, whereas MP reduced the survival of activated CD4(+) T cells and could inhibit the survival effects of poly I:C and CpG DNA. The NF-kappa B essential modifier-binding domain (NBD) inhibited the survival of activated CD4(+) T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor crucumin did not have the same effect. The increased expression of NF-kappa B induced by poly I:C and CpG DNA in activated CD4(+) T cells could be inhibited by MP, but the same was not true for the increased expression of AP-1 induced by poly I:C and CpG DNA. Finally, the proliferation of activated CD4(+) T cells was not affected by poly I:C or MP. CONCLUSION: The survival of activated CD4(+) T cells is promoted by TLR ligands, but this effect is inhibited by MP.展开更多
Objective: The combination of highly active antiretroviral therapy (HAART) and chemotherapy with ABV regimen (doxorubicin, bleomycin and vincristine) is a promising approach for the treatment of advanced HIV-related K...Objective: The combination of highly active antiretroviral therapy (HAART) and chemotherapy with ABV regimen (doxorubicin, bleomycin and vincristine) is a promising approach for the treatment of advanced HIV-related Kaposi's sarcoma (KS). Here we analyzed the relationship between the CD4 lymphocyte cell count and the clinical response to chemotherapy. Methods: The 176 HIV infected patients with advanced KS who failed to respond to prior HAART were selected. All these patients were then preceded to chemotherapy with ABV regimen which was administered at 3 weekly intervals for 6 cycles. For each patient CD4 cell count was done before starting chemotherapy and after finishing 6 cycles of chemotherapy. The difference of CD4 cell counts pre chemotherapy and post chemotherapy was compared with the clinical progress of the patients after 6 cycles of chemotherapy. Results: The overall clinical remission was shown in 93.7% patients. Progressive disease (PD) and no change in clinical condition (NC) was shown in 6.3% patients. The increase in CD4 cell count post chemotherapy was found in 89.8% patients and the decrease in CD4 cell count was seen in 10.2% patients. The difference of the mean CD4 cell counts for patients in group CR + PR (complete relief + partial relief) before and after chemotherapy was highly significant. The difference of the mean CD4 cell counts for patients in group NC + PD before and after chemotherapy was not significant. The difference in CD4 cell counts in CR + PR and NC + PD groups before and after chemotherapy was highly significant. Conclusion: The HIV related KS patients on HAART benefit from the chemotherapy as it increases the CD4 cell count and it has positive impact on clinical remission of KS.展开更多
BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present ...BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS: Male Sprague Dawley rats were randomly divided into 3 treatment groups (n=6, each): sham-operated, vehicle (normal saline)+TBI, and PACAP+TBI. Normal saline or PACAP (1 μg/5 μL) was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4+ and CD8+ T cells in blood and the spleen were detected via flow cytometry.RESULTS: In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4+ CD8+ lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBl+vehicle, and CD4- CD8+ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4+, and decreased CD8+, T lymphocytes in blood and the spleen.CONCLUSION: Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.展开更多
In the present paper we have observed the effect of discontinuous gradient two-step Percoll centrifugation on depleting mature T lymphocytes from normal bone marrow. The pre-/post-Percoll percentage of CD34+, and Leu4...In the present paper we have observed the effect of discontinuous gradient two-step Percoll centrifugation on depleting mature T lymphocytes from normal bone marrow. The pre-/post-Percoll percentage of CD34+, and Leu4+ cells in MNC was counted by using APAAP technique. As the two-step Percoll centrifugation is simple,and time saving, and decreases the incidence of contamination of cultured cells as well,This technique may be of value in serum-free culture of hematopoietic cells and immunological studies.展开更多
Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently...Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently healthy prospective whole blood donors. Participants and Methods: This was a hospital based prospective study carried out from August to October 2020 at the blood transfusion unit of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria. A structured pretested questionnaire was used for data collection. The socio demographic status and the haematology parameters of apparently healthy prospective whole blood donors who tested negative for HIV, hepatitis B and C markers were captured. Obtained data were analysed with the statistical package for the social scientist software version 20. Results: One hundred male (97.1%) and three female (2.9%) apparently healthy prospective whole blood donors were studied. The median age of study subjects was 30 years. Obtained median haematology parameter values were 13 g/dl, 40%, 4.9/nl and 203.9/nl for haemoglobin concentration, haematocrit, total white cell and platelet counts respectively. The median values for the mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) of participants were 32.6 g/dl, 27.7 pg and 85.7 fl respectively. Observed prevalence of subnormal haematology parameters for haemoglobin concentration, total white cells, platelets were 12.6%, 25.2%, and 13.6% respectively. Also subnormal values for MCHC, MCH, MCV were 11.7%, 26.2%, and 16.5% respectively among prospective whole blood donors in this study. No higher than normal haematology parameter values were observed. Median values for erythrocyte sedimentation rate was 8.4 mm/hr. Conclusion: A significant percentage of apparently healthy prospective whole blood donors had subnormal haematology parameters values. Obtained normal values in our study are comparable with local reference range reports from previous studies in Nigeria and other parts of Africa. 124947 .展开更多
BACKGROUND: The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoho...BACKGROUND: The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease (NAFLD). METHODS: We analyzed differentially expressed microRNA and mRNA expression profiles of CD4+ T lymphocytes from the liver and mesenteric lymph nodes (MLNs) of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls. The target genes of microRNAs were predicted by TargetScan. Integrative analysis showed that the mRNAs were overlapped with microRNAs. Furthermore, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the key genes and pathways. Then, 16 microRNAs and 10 mRNAs were validated by qRT-PCR. RESULTS: Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4+ T lymphocytes from the liver between the two groups. Eighty mRNAs corresponded with microRNA targeted genes. KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice. miR-23b, let-7e, miR-128 and miR-130b possibly played significant parts in the MAPK pathways. Furthermore, between the two groups, 237 microRNAs were significantly deregulated in CD4+ T lymphocytes from MLNs. 38 mRNAs coincided with microRNA target genes. The metabolic pathway was consistently enriched in the MLNs of NAFLD mice. miR- 206-3p, miR-181a-Sp, miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways. CONCLUSION: The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.展开更多
Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unk...Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unknown.A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas,elevated IgG levels,and negative autoimmune antibody responses.A pylorus-preserving pancreatoduodenectomy was per-formed and a pancreatic tumor was suspected.Howev-er,periductal lymphoplasmacytic inf iltration and f ibrosis were found in the head of pancreas and nearby organs instead of tumor cells.Four months after surgery,the patient was readmitted because of reoccurrence ofsevere jaundice and sustained abdominal distension.Prednisone 30 mg/d was administered orally as an AIP was suspected.One and a half months later,the symp-toms of the patient disappeared,and globulin,amino-transferase and bilirubin levels decreased signif icantly.Over a 9-mo follow-up period,the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition.We further demonstrated dominant CD3+/CD8+ populations,CD20+ cells and a few CD4+ cells in the pancreatic parenchyma,duo-denum and gallbladder wall by immunohistochemical assay.This AIP case presented with signif icant CD8+ T lymphocyte inf iltration in the pancreas and extra-pan-creatic lesions,indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.展开更多
Objective To evaluate the prevalence of CD4 ^+ CD25^high regulatory T cells ( Treg cells) in the peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) of patients with non-small cel...Objective To evaluate the prevalence of CD4 ^+ CD25^high regulatory T cells ( Treg cells) in the peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) of patients with non-small cell lung cancer (NSCLC) and to investigate immunosuppression to the progression of cancer. Methods Peripheral blood and tumor tissues were collected from 20 patients with NSCLC at the time of surgery. None of the patients received surgery, radiotherapy, chemotherapy, or other medical interventions before this study. Cancer stages of the patients were Ⅰ-Ⅲ A. Venous blood samples were obtained from 20 health donors. PBMC were isolated from blood samples by differential centrifugation over Ficoll-Hypaque. TILs were isolated from tumors by differential centrifugation over Ficoll-Hypaque and Percoll. Percentage of CD4^+ CD25^highTr/CD4+T in PBMC and TIL was assessed by the flow cytometry. Results The percentage of CD4^ + CD25high Tr/ CD4 ^+T in PBMC [ (4. 87 ± 1.22 ) % ] of NSCLC patients was significantly higher than that in healthy donors [ ( 2.36 ± 0. 72 ) % ] ( P 〈 0.01 ). The percentage of CD4^+ CD25^highTr/ CD4^+ T in PBMC [ (5.40 ± 1.20) % ] of NSCLC patients in stage Ⅱ-Ⅲ A was significantly higher than that in stage Ⅰ [ (3. 87 ± 0. 22 ) % ] ( P 〈 0. 01 ). The percentage of CD4 + CD25hiShTr/ CD4 + T in TIL[ ( 8. 66 ±0. 76) % ] of NSCLC patients in stage Ⅱ-Ⅲ A was significantly higher than that in stage Ⅰ [ ( 7. 04 ± 0. 80) % ] ( P 〈 0. 01 ). Conclusion The prevalence of CD4 ^+ CD25^highTreg cells in PBMC and TIL of NSCLC patients was significantly higher than that in healthy donors. These Treg cells may be preventing appropriate antitumor immune responses. The population of CD4^ + CD25^highTreg cells in PBMC and TILs of NSCLC patients with Ⅱ-Ⅲ A stage was significantly higher than that of NSCLC patients with Ⅰ stage. These Treg cells may facilitate development of tumors.展开更多
Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play...Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.展开更多
Signal transducers and activators of transcription 5(Stat5)is known to engage in regulating the differentiation and effector function of various subsets of T helper cells.However,how Stat5 regulates the antitumor acti...Signal transducers and activators of transcription 5(Stat5)is known to engage in regulating the differentiation and effector function of various subsets of T helper cells.However,how Stat5 regulates the antitumor activity of tumor-infiltrating CD4^(+)T cells is largely unknown.Here,we showed that mice with specific deletion of Stat5 in CD4^(+)T cells were less susceptible to developing subcutaneous and lung metastatic B16 melanoma with CD4^(+)tumor-infiltrating lymphocytes(TILs)remolding.Especially,we confirmed that Stat5-deficient CD4^(+)naïve T cells were prone to polarization of two subtypes of Th17 cells:IFN-γ^(+)and IFN-γ^(-)Th17 cells,which exhibited increased anti-melanoma activity through enhanced activation of Notch1 pathway compared with wild type Th17 cells.Our study therefore revealed a novel function of Stat5 in regulating tumor-specific Th17 cell differentiation and function in melanoma.This study also provided a new possibility for targeting Stat5 and other Th17-associated pathways to develop novel immunotherapies for melanoma patients.展开更多
activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe...activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe that CD70 expression distinguishes proinflammatory CD4^(+)T lymphocytes that display an increased potential to migrate into the central nervous system(CNS).Upregulation of CD70 on CD4^(+)T lymphocytes is induced by TGF-β1 and TGF-β3,which promote a pathogenic phenotype.In addition,CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γexpression by both T helper subtypes.Moreover,adoptive transfer of CD70−/−CD4^(+)T lymphocytes induced less severe experimental autoimmune encephalomyelitis(EAE)disease than transfer of WT CD4^(+)T lymphocytes.CD70+CD4^(+)T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice,highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.展开更多
OBJECTIVE:To observe the effects of Xinfeng capsule on the apoptosis of peripheral blood CD4+ T lymphocytes and changes in the Fas/Fas L-mediated apoptotic pathway in patients with rheumatoid arthritis(RA).METHODS:A t...OBJECTIVE:To observe the effects of Xinfeng capsule on the apoptosis of peripheral blood CD4+ T lymphocytes and changes in the Fas/Fas L-mediated apoptotic pathway in patients with rheumatoid arthritis(RA).METHODS:A total of 28 RA patients were included in the study;they were randomly divided into the Xinfeng capsule(XFC) group(3 capsules,3 per day)and the leflunomide(LEF) group(1 pellet,once per night).The treatment course in each groups was 12 weeks.The normal control(NC) group consisted of10 healthy people.The apoptotic rate was examined using flow cytometry.Fas,Fas L,caspase 8,caspase 3,bcl-2,and bax m RNA were examined using q RT-PCR.Apoptotic proteins Fas,Fas L,caspase8,and caspase 3 were examined using western blotting.RESULTS:After treatment,patients in the two groups all showed some trend of improvement.Disease activity indexes,joint morning stiffness time,joint swelling/tenderness number,health assessment questionnaire(HAQ) score,RA quality of life(RAQOL) questionnaire,and self-rating anxiety scale(SAS),as well as all apoptotic related indicators were reduced in both groups after treatment with no significant difference between groups.But the improvement in terms of the self-rating depression scale(SDS) in the XFC group was better than in the LEF group.RA patients showed lower apoptotic rates in CD4+ T cells,lower bax,Fas,caspase 8,and caspase 3 m RNA,and less protein expression of Fas,caspase 8,and caspase3 than in the NC group.These indicators increased after treatment.However,the level of Bcl-2 m RNA was higher in the XFC group than in the NC group before treatment,and it subsequently decreased.The XFC group expressed lower Bcl-2 m RNA than the LEF group.Negative correlations were found between ESR and the apoptotic rate in CD4 + T cells,Fas,and caspase 3;CRP and Fas;and,swollen joint count and Bax,while positive correlations were found between ESR and Bcl-2.CONCLUSION:XFC can regulate the Fas/Fas L system and promote CD4+ T cell apoptosis and thus reduce the abnormal immune response,which can improve symptoms in RA patients.展开更多
Background Highly active antiretroviral therapy (HAART) produces profound suppression of HIV replication, substantial increase in CD4^+ T cells, and partial reconstitution of the immune system. However, the numbers...Background Highly active antiretroviral therapy (HAART) produces profound suppression of HIV replication, substantial increase in CD4^+ T cells, and partial reconstitution of the immune system. However, the numbers of subjects were small in previous Chinese studies. This study evaluated the efficacy and side effects of HAART in Chinese advanced AIDS patients.Methods One hundred and three antiretroviral drug naive AIDS patients were enrolled in this study and were divided into two groups by their baseline CD4^+ count: 〈 100 cells/μl or ≥ 100 cells/μl. Clinical, virological and immunological outcomes were monitored at baseline and at 1, 3, 6, 9 and 12 months during the course of treatment with HAART.Results One patient died and another was lost from the follow-up. For the remaining 101 HIV/AIDS patients at the 12th month during the HAART, the plasma viral load (VL) was reduced to (3.2±0.7) lg copies/ml, the CD4^+ count increased to (168 ±51) cells/μl [among which the naive phenotype (CD45RA^+CD62L^+) increased to (49 ±27) cells/μl and the memory phenotype (CD45RA^-) increased to (119 ±55) cells/μl], and the percentage of CD4^+CD28^+ cells increased. At the same time, there was a significant reduction of CD8^+ T cell activation. In the 69 patients with the baseline CD4^+ count 〈100 cells/μl, 37 had a VL 〈50 copies/ml; while in the 34 patients with the baseline CD4^+ count ≥ 100 cells/μl, 25 had a VL 〈50 copies/ml, the difference between the two groups was statistically significant. The CD4^+ T cell count showed a two-phase increase during HAART and a significant positive correlation was shown between the change of CD4^+ count and plasma VL. Over 12 months of HAART, 10 patients had gastrointestinal side effects, 13 peripheral neuritis, 7 hepatic lesions, 8 hematological side effects, 8 skin rashes, 10 lipodystrophy and 1 renal calculus.Conclusions Immune reconstitution as well as the significantly improved clinical outcomes is observed in Chinese advanced AIDS patients after HAART. Side effects are common during HAART and require clinical attention.展开更多
Objective:In this study,we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome(AIDS)and human immunodeficiency virus(HIV)-positive individuals(...Objective:In this study,we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome(AIDS)and human immunodeficiency virus(HIV)-positive individuals(AIDS/HIV patients),and explored the relationships among intestinal flora,peripheral blood inflammatory factors,and CD4^+T lymphocytes.Methods:Thirty blood and stool samples from an AIDS group and a control group were collected.The levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were determined by enzyme-linked immunosorbent assay(ELISA),and the number of CD4^+T lymphocytes by a FACSCount automated instrument.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to determine the messenger RNA(mRNA)levels of Bifidobacterium,Lactobacillus,Escherichia coli,Enterococcus faecalis,and Enterococcus faecium.Correlations among intestinal flora,inflammatory factor levels,and CD4^+T lymphocyte values were evaluated using the Spearman correlation coefficient.Results:The levels of TNF-αand IL-6 in the AIDS group were higher than those in the control group,while the number of CD4^+T lymphocytes was lower.The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group,while the amounts of E.coli,E.faecalis,and E.faecium were much higher.The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-αand IL-6 and the CD4^+T lymphocyte count,while those correlations were reversed for E.coli,E.faecalis,and E.faecium.Conclusions:The intestinal microbiota of AIDS/HIV patients were disordered,and there was a correlation between the amount of intestinal flora and the number of CD4^+T lymphocytes and the levels of TNF-αand IL-6.展开更多
基金Supported by a liver disease research foundation for the young and middle aged scientistsChinese Medical Association
文摘AIM:To explore a novel mechanism for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), upregulation of CD4+ and CD8+T lymphocytes participating in the patho-physiological process of chronic hepatitis B (CHB). METHODS: The levels of serum soluble TRAIL (sTRAIL), serum IFN-γ and membrane-bound TRAIL expression on peripheral leucocytes from 58 CHB patients were examined by ELISA and flow cytometry respectively. The levels of TRAIL were compared with the baseline levels of 17 healthy controls, and correlation analysis was performed between ALT, TBIL, PT, morphological change in hepatic tissues, and serum IFN-γ. RESULTS: The results showed that TRAIL levels on membranes of CD4+, CD8+ T cells in CHB patients were much higher than those in healthy controls (P<0.001), and were correlated with serum TBIL (r=0.354, P= 0.008 for CD4+ and r= 0.522, P= 0.000 for CD8+, respectively), ALT (r= 0.393, P= 0.003 for CD8+), PT (r = 0.385, P = 0.004 for CD8+) and serum IFN-y level (r = 0.302, P= 0.011 for CD4+ and r= 0.307, P= 0.009 for CD8+). On the contrary to membrane-bound TRAIL expression, serum level of sTRAIL was not correlated with that of TBIL and PT, though it was higher than that of the normal population and was positively correlated with serum HBeAg expression (r= 0.695, P = 0.001). CONCLUSION: The expression level of TRAIL on the membrane of lymphocytes was upregulated and associated with the liver injury in CHB patients. These findings suggest that upregulation of TRAIL expression may be induced by virus antigen and inflammatory cytokine IFN-γ.
文摘The function of CD4+CD25+ regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-β1 and IFN-γ) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P〈0.01), the inhibitory ability of Treg on the T lymphocytes proliferation was reduced (P〈0.01), IFN-γ levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-γ was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.
文摘BACKGROUND: Methylprednisolone (MP) can affect the survival of CD4(+) T lymphocytes and plays an important role in adaptive immune responses; however, its mechanism of action is not clear. Recent studies have shown that toll-like receptors (TLRs) on CD4(+) T cells can directly modulate adaptive immune responses by affecting the survival and proliferation of activated CD4(+) T cells. This study aimed to investigate the relationship between MP, TLRs and activated CD4(+) T cells. METHODS: We separated and purified CD4(+) T cells from mice, activated them in vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1). We then assessed CD4(+) T cell survival and proliferation and the expression of NF-kappa B and AP-1. RESULTS: Activated CD4(+) T cells showed increased TLR-3 and TLR-9 mRNA expression, but polyinosinic-polycytidylic acid (poly I:C) and MP had no effect on the expression of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased the survival of activated CD4(+) T cells, whereas MP reduced the survival of activated CD4(+) T cells and could inhibit the survival effects of poly I:C and CpG DNA. The NF-kappa B essential modifier-binding domain (NBD) inhibited the survival of activated CD4(+) T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor crucumin did not have the same effect. The increased expression of NF-kappa B induced by poly I:C and CpG DNA in activated CD4(+) T cells could be inhibited by MP, but the same was not true for the increased expression of AP-1 induced by poly I:C and CpG DNA. Finally, the proliferation of activated CD4(+) T cells was not affected by poly I:C or MP. CONCLUSION: The survival of activated CD4(+) T cells is promoted by TLR ligands, but this effect is inhibited by MP.
文摘Objective: The combination of highly active antiretroviral therapy (HAART) and chemotherapy with ABV regimen (doxorubicin, bleomycin and vincristine) is a promising approach for the treatment of advanced HIV-related Kaposi's sarcoma (KS). Here we analyzed the relationship between the CD4 lymphocyte cell count and the clinical response to chemotherapy. Methods: The 176 HIV infected patients with advanced KS who failed to respond to prior HAART were selected. All these patients were then preceded to chemotherapy with ABV regimen which was administered at 3 weekly intervals for 6 cycles. For each patient CD4 cell count was done before starting chemotherapy and after finishing 6 cycles of chemotherapy. The difference of CD4 cell counts pre chemotherapy and post chemotherapy was compared with the clinical progress of the patients after 6 cycles of chemotherapy. Results: The overall clinical remission was shown in 93.7% patients. Progressive disease (PD) and no change in clinical condition (NC) was shown in 6.3% patients. The increase in CD4 cell count post chemotherapy was found in 89.8% patients and the decrease in CD4 cell count was seen in 10.2% patients. The difference of the mean CD4 cell counts for patients in group CR + PR (complete relief + partial relief) before and after chemotherapy was highly significant. The difference of the mean CD4 cell counts for patients in group NC + PD before and after chemotherapy was not significant. The difference in CD4 cell counts in CR + PR and NC + PD groups before and after chemotherapy was highly significant. Conclusion: The HIV related KS patients on HAART benefit from the chemotherapy as it increases the CD4 cell count and it has positive impact on clinical remission of KS.
文摘BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS: Male Sprague Dawley rats were randomly divided into 3 treatment groups (n=6, each): sham-operated, vehicle (normal saline)+TBI, and PACAP+TBI. Normal saline or PACAP (1 μg/5 μL) was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4+ and CD8+ T cells in blood and the spleen were detected via flow cytometry.RESULTS: In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4+ CD8+ lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBl+vehicle, and CD4- CD8+ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4+, and decreased CD8+, T lymphocytes in blood and the spleen.CONCLUSION: Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.
文摘In the present paper we have observed the effect of discontinuous gradient two-step Percoll centrifugation on depleting mature T lymphocytes from normal bone marrow. The pre-/post-Percoll percentage of CD34+, and Leu4+ cells in MNC was counted by using APAAP technique. As the two-step Percoll centrifugation is simple,and time saving, and decreases the incidence of contamination of cultured cells as well,This technique may be of value in serum-free culture of hematopoietic cells and immunological studies.
文摘Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently healthy prospective whole blood donors. Participants and Methods: This was a hospital based prospective study carried out from August to October 2020 at the blood transfusion unit of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria. A structured pretested questionnaire was used for data collection. The socio demographic status and the haematology parameters of apparently healthy prospective whole blood donors who tested negative for HIV, hepatitis B and C markers were captured. Obtained data were analysed with the statistical package for the social scientist software version 20. Results: One hundred male (97.1%) and three female (2.9%) apparently healthy prospective whole blood donors were studied. The median age of study subjects was 30 years. Obtained median haematology parameter values were 13 g/dl, 40%, 4.9/nl and 203.9/nl for haemoglobin concentration, haematocrit, total white cell and platelet counts respectively. The median values for the mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) of participants were 32.6 g/dl, 27.7 pg and 85.7 fl respectively. Observed prevalence of subnormal haematology parameters for haemoglobin concentration, total white cells, platelets were 12.6%, 25.2%, and 13.6% respectively. Also subnormal values for MCHC, MCH, MCV were 11.7%, 26.2%, and 16.5% respectively among prospective whole blood donors in this study. No higher than normal haematology parameter values were observed. Median values for erythrocyte sedimentation rate was 8.4 mm/hr. Conclusion: A significant percentage of apparently healthy prospective whole blood donors had subnormal haematology parameters values. Obtained normal values in our study are comparable with local reference range reports from previous studies in Nigeria and other parts of Africa. 124947 .
基金supported by a grant from the National Natural Science Foundation of China(81170375)
文摘BACKGROUND: The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease (NAFLD). METHODS: We analyzed differentially expressed microRNA and mRNA expression profiles of CD4+ T lymphocytes from the liver and mesenteric lymph nodes (MLNs) of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls. The target genes of microRNAs were predicted by TargetScan. Integrative analysis showed that the mRNAs were overlapped with microRNAs. Furthermore, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the key genes and pathways. Then, 16 microRNAs and 10 mRNAs were validated by qRT-PCR. RESULTS: Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4+ T lymphocytes from the liver between the two groups. Eighty mRNAs corresponded with microRNA targeted genes. KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice. miR-23b, let-7e, miR-128 and miR-130b possibly played significant parts in the MAPK pathways. Furthermore, between the two groups, 237 microRNAs were significantly deregulated in CD4+ T lymphocytes from MLNs. 38 mRNAs coincided with microRNA target genes. The metabolic pathway was consistently enriched in the MLNs of NAFLD mice. miR- 206-3p, miR-181a-Sp, miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways. CONCLUSION: The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.
文摘Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unknown.A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas,elevated IgG levels,and negative autoimmune antibody responses.A pylorus-preserving pancreatoduodenectomy was per-formed and a pancreatic tumor was suspected.Howev-er,periductal lymphoplasmacytic inf iltration and f ibrosis were found in the head of pancreas and nearby organs instead of tumor cells.Four months after surgery,the patient was readmitted because of reoccurrence ofsevere jaundice and sustained abdominal distension.Prednisone 30 mg/d was administered orally as an AIP was suspected.One and a half months later,the symp-toms of the patient disappeared,and globulin,amino-transferase and bilirubin levels decreased signif icantly.Over a 9-mo follow-up period,the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition.We further demonstrated dominant CD3+/CD8+ populations,CD20+ cells and a few CD4+ cells in the pancreatic parenchyma,duo-denum and gallbladder wall by immunohistochemical assay.This AIP case presented with signif icant CD8+ T lymphocyte inf iltration in the pancreas and extra-pan-creatic lesions,indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.
基金Supported by the Natural Science Foundation of Shanghai,China(04ZR14109)
文摘Objective To evaluate the prevalence of CD4 ^+ CD25^high regulatory T cells ( Treg cells) in the peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) of patients with non-small cell lung cancer (NSCLC) and to investigate immunosuppression to the progression of cancer. Methods Peripheral blood and tumor tissues were collected from 20 patients with NSCLC at the time of surgery. None of the patients received surgery, radiotherapy, chemotherapy, or other medical interventions before this study. Cancer stages of the patients were Ⅰ-Ⅲ A. Venous blood samples were obtained from 20 health donors. PBMC were isolated from blood samples by differential centrifugation over Ficoll-Hypaque. TILs were isolated from tumors by differential centrifugation over Ficoll-Hypaque and Percoll. Percentage of CD4^+ CD25^highTr/CD4+T in PBMC and TIL was assessed by the flow cytometry. Results The percentage of CD4^ + CD25high Tr/ CD4 ^+T in PBMC [ (4. 87 ± 1.22 ) % ] of NSCLC patients was significantly higher than that in healthy donors [ ( 2.36 ± 0. 72 ) % ] ( P 〈 0.01 ). The percentage of CD4^+ CD25^highTr/ CD4^+ T in PBMC [ (5.40 ± 1.20) % ] of NSCLC patients in stage Ⅱ-Ⅲ A was significantly higher than that in stage Ⅰ [ (3. 87 ± 0. 22 ) % ] ( P 〈 0. 01 ). The percentage of CD4 + CD25hiShTr/ CD4 + T in TIL[ ( 8. 66 ±0. 76) % ] of NSCLC patients in stage Ⅱ-Ⅲ A was significantly higher than that in stage Ⅰ [ ( 7. 04 ± 0. 80) % ] ( P 〈 0. 01 ). Conclusion The prevalence of CD4 ^+ CD25^highTreg cells in PBMC and TIL of NSCLC patients was significantly higher than that in healthy donors. These Treg cells may be preventing appropriate antitumor immune responses. The population of CD4^ + CD25^highTreg cells in PBMC and TILs of NSCLC patients with Ⅱ-Ⅲ A stage was significantly higher than that of NSCLC patients with Ⅰ stage. These Treg cells may facilitate development of tumors.
基金supported by the National Key R&D Program of China(Grant nos.2018YFC1311500(B.S.),2017YFC0907500(K.Y.)and 2018YFC0910400(K.Y.))National Science Foundation of China(NSFC)(Grant nos.81970679(B.S.),81500690(Y.W.),and 31671372(K.Y.))+3 种基金Natural Science Foundation of Shaanxi Province(2018JM70990(Y.W.))Key Research and Development Project of Shaanxi Province(Grant no.2017ZDXM-SF-060(B.S.))Fundamental Research Funds for the Central Universities(1191329875(Y.W.))the China Postdoctoral Science Foundation(224646(Y.W.)).
文摘Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.
基金supported by start-up funds for Prof. Xin-Yuan Fu (139170082)sponsored by West China Hospital, Sichuan Universityin part by the Chinese National Natural Science Funds (81902947)。
文摘Signal transducers and activators of transcription 5(Stat5)is known to engage in regulating the differentiation and effector function of various subsets of T helper cells.However,how Stat5 regulates the antitumor activity of tumor-infiltrating CD4^(+)T cells is largely unknown.Here,we showed that mice with specific deletion of Stat5 in CD4^(+)T cells were less susceptible to developing subcutaneous and lung metastatic B16 melanoma with CD4^(+)tumor-infiltrating lymphocytes(TILs)remolding.Especially,we confirmed that Stat5-deficient CD4^(+)naïve T cells were prone to polarization of two subtypes of Th17 cells:IFN-γ^(+)and IFN-γ^(-)Th17 cells,which exhibited increased anti-melanoma activity through enhanced activation of Notch1 pathway compared with wild type Th17 cells.Our study therefore revealed a novel function of Stat5 in regulating tumor-specific Th17 cell differentiation and function in melanoma.This study also provided a new possibility for targeting Stat5 and other Th17-associated pathways to develop novel immunotherapies for melanoma patients.
基金T.D.holds a fellowship from the Fonds de Recherche du Québec-Santé(FRQS).L.T.holds scholarships from Universitéde Montréal and CRCHUM.E.P.holds a fellowship from the Multiple Sclerosis Society of Canada(MSSC)and the FRQS.S.Z.is supported by a fellowship from Biogen Canada.C.L.is supported by FRQS.A.P.holds the T1(senior)Canada Research Chair in Multiple Sclerosis.This work was funded by operating grants from the Canadian Institutes of Health Research(MOP 89885,PJI-153195)and from the MSSC(EGID 2382).We thank Jannie Borst for providing us with the CD70−/−mice.We thank Hartmut Wekerle for providing us with the TCR1640 mice.Special thanks to Magdalena Paterka and Volker Siffrin for providing the protocol for CD4+adoptive T cell transfer in RAG null mice.We would also like to thank the imaging platform,the pathology platform,and the flow cytometry platform from the CRCHUM for the excellent technical support and Alice M Roy and Elvia Gonzalez for their excellent technical animal support.
文摘activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe that CD70 expression distinguishes proinflammatory CD4^(+)T lymphocytes that display an increased potential to migrate into the central nervous system(CNS).Upregulation of CD70 on CD4^(+)T lymphocytes is induced by TGF-β1 and TGF-β3,which promote a pathogenic phenotype.In addition,CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γexpression by both T helper subtypes.Moreover,adoptive transfer of CD70−/−CD4^(+)T lymphocytes induced less severe experimental autoimmune encephalomyelitis(EAE)disease than transfer of WT CD4^(+)T lymphocytes.CD70+CD4^(+)T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice,highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.
基金the Key Projects in the National Science & Technology Pillar Program in the Twelfth Five-Year Plan Period:Clinical Research on Xin'an Medicine Prevention and Treatment of Difficult Diseases(No.2012BAI26B02)
文摘OBJECTIVE:To observe the effects of Xinfeng capsule on the apoptosis of peripheral blood CD4+ T lymphocytes and changes in the Fas/Fas L-mediated apoptotic pathway in patients with rheumatoid arthritis(RA).METHODS:A total of 28 RA patients were included in the study;they were randomly divided into the Xinfeng capsule(XFC) group(3 capsules,3 per day)and the leflunomide(LEF) group(1 pellet,once per night).The treatment course in each groups was 12 weeks.The normal control(NC) group consisted of10 healthy people.The apoptotic rate was examined using flow cytometry.Fas,Fas L,caspase 8,caspase 3,bcl-2,and bax m RNA were examined using q RT-PCR.Apoptotic proteins Fas,Fas L,caspase8,and caspase 3 were examined using western blotting.RESULTS:After treatment,patients in the two groups all showed some trend of improvement.Disease activity indexes,joint morning stiffness time,joint swelling/tenderness number,health assessment questionnaire(HAQ) score,RA quality of life(RAQOL) questionnaire,and self-rating anxiety scale(SAS),as well as all apoptotic related indicators were reduced in both groups after treatment with no significant difference between groups.But the improvement in terms of the self-rating depression scale(SDS) in the XFC group was better than in the LEF group.RA patients showed lower apoptotic rates in CD4+ T cells,lower bax,Fas,caspase 8,and caspase 3 m RNA,and less protein expression of Fas,caspase 8,and caspase3 than in the NC group.These indicators increased after treatment.However,the level of Bcl-2 m RNA was higher in the XFC group than in the NC group before treatment,and it subsequently decreased.The XFC group expressed lower Bcl-2 m RNA than the LEF group.Negative correlations were found between ESR and the apoptotic rate in CD4 + T cells,Fas,and caspase 3;CRP and Fas;and,swollen joint count and Bax,while positive correlations were found between ESR and Bcl-2.CONCLUSION:XFC can regulate the Fas/Fas L system and promote CD4+ T cell apoptosis and thus reduce the abnormal immune response,which can improve symptoms in RA patients.
基金This study was supported by the grants from the National Key Technologies R&D Program for the 10th Five-Year Plan (No. 2004BA719A10), the HIV/AIDS Prevention and Treatment Project of Ministry of Health (No. WA2003-05), and the Critical Clinical Project of Ministry of Health.
文摘Background Highly active antiretroviral therapy (HAART) produces profound suppression of HIV replication, substantial increase in CD4^+ T cells, and partial reconstitution of the immune system. However, the numbers of subjects were small in previous Chinese studies. This study evaluated the efficacy and side effects of HAART in Chinese advanced AIDS patients.Methods One hundred and three antiretroviral drug naive AIDS patients were enrolled in this study and were divided into two groups by their baseline CD4^+ count: 〈 100 cells/μl or ≥ 100 cells/μl. Clinical, virological and immunological outcomes were monitored at baseline and at 1, 3, 6, 9 and 12 months during the course of treatment with HAART.Results One patient died and another was lost from the follow-up. For the remaining 101 HIV/AIDS patients at the 12th month during the HAART, the plasma viral load (VL) was reduced to (3.2±0.7) lg copies/ml, the CD4^+ count increased to (168 ±51) cells/μl [among which the naive phenotype (CD45RA^+CD62L^+) increased to (49 ±27) cells/μl and the memory phenotype (CD45RA^-) increased to (119 ±55) cells/μl], and the percentage of CD4^+CD28^+ cells increased. At the same time, there was a significant reduction of CD8^+ T cell activation. In the 69 patients with the baseline CD4^+ count 〈100 cells/μl, 37 had a VL 〈50 copies/ml; while in the 34 patients with the baseline CD4^+ count ≥ 100 cells/μl, 25 had a VL 〈50 copies/ml, the difference between the two groups was statistically significant. The CD4^+ T cell count showed a two-phase increase during HAART and a significant positive correlation was shown between the change of CD4^+ count and plasma VL. Over 12 months of HAART, 10 patients had gastrointestinal side effects, 13 peripheral neuritis, 7 hepatic lesions, 8 hematological side effects, 8 skin rashes, 10 lipodystrophy and 1 renal calculus.Conclusions Immune reconstitution as well as the significantly improved clinical outcomes is observed in Chinese advanced AIDS patients after HAART. Side effects are common during HAART and require clinical attention.
文摘Objective:In this study,we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome(AIDS)and human immunodeficiency virus(HIV)-positive individuals(AIDS/HIV patients),and explored the relationships among intestinal flora,peripheral blood inflammatory factors,and CD4^+T lymphocytes.Methods:Thirty blood and stool samples from an AIDS group and a control group were collected.The levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were determined by enzyme-linked immunosorbent assay(ELISA),and the number of CD4^+T lymphocytes by a FACSCount automated instrument.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to determine the messenger RNA(mRNA)levels of Bifidobacterium,Lactobacillus,Escherichia coli,Enterococcus faecalis,and Enterococcus faecium.Correlations among intestinal flora,inflammatory factor levels,and CD4^+T lymphocyte values were evaluated using the Spearman correlation coefficient.Results:The levels of TNF-αand IL-6 in the AIDS group were higher than those in the control group,while the number of CD4^+T lymphocytes was lower.The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group,while the amounts of E.coli,E.faecalis,and E.faecium were much higher.The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-αand IL-6 and the CD4^+T lymphocyte count,while those correlations were reversed for E.coli,E.faecalis,and E.faecium.Conclusions:The intestinal microbiota of AIDS/HIV patients were disordered,and there was a correlation between the amount of intestinal flora and the number of CD4^+T lymphocytes and the levels of TNF-αand IL-6.