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Association between TRAIL expression on peripheral blood lymphocytes and liver damage in chronic hepatitis B 被引量:6
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作者 Gong-YingChen Jian-QinHe +5 位作者 Guo-CaiLu Ming-WeiLi Chen-HuaiXu Wei-WeiFan ChenZhou ZhiChen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第26期4090-4093,共4页
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
关键词 HBV CD8+ lymphocyte cd4+ lymphocyte TRAIL Liver function
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Changes of CD4^+CD25^+ Regulatory T Cells in Patients with Acute Coronary Syndrome and the Effects of Atorvastatin 被引量:10
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作者 胡珍娉 李大主 +1 位作者 胡英锋 杨克平 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2007年第5期524-527,共4页
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
关键词 acute coronary syndrome regulatory cd4^+CD25^+ T lymphocytes CYTOKINE ATORVASTATIN
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Methylprednisolone inhibits activated CD4^+ T cell survival promoted by toll-like receptor ligands 被引量:3
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作者 Lu, You-Sheng Pu, Li-Yong +1 位作者 Li, Xiang-Cheng Wang, Xue-Hao 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2010年第4期376-383,共8页
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
关键词 METHYLPREDNISOLONE toll-like receptor cd4(+) T lymphocytes NF-kappa B
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The effect of ABV regimen on CD4 lymphocyte count in patients with advanced HIV related Kaposi’s sarcoma 被引量:1
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作者 Lin Lin Datta Dharmadhikari Alexander von Paleske 《The Chinese-German Journal of Clinical Oncology》 CAS 2011年第6期366-368,共3页
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
关键词 lymphocyte cd4 CHEMOTHERAPY AIDS highly active antiretroviral therapy (HAART) Kaposi's sarcoma (KS)
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Effects of pituitary adenylate cyclase activating polypeptide on CD4^+/CD8^+T cell levels after traumatic brain injury in a rat model 被引量:2
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作者 Rong Hua Shan-shan Mao +3 位作者 Yong-mei Zhang Fu-xing Chen Zhong-hai Zhou Jun-quan Liu 《World Journal of Emergency Medicine》 CAS 2012年第4期294-298,共5页
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
关键词 Traumatic brain injury Pituitary adenylate cyclase activating polypeptide cd4^+T lymphocyte CD8^+T lymphocyte Rat SPLEEN Blood Flow cytometry
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An Effective Method for Depleting MatureT Lymphocytes from Bone Marrow Cells──Two-step Percoll Centrifugation
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作者 唐继森 王辨明 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 1994年第2期128-128,共1页
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
关键词 Percoll centrifugation mature T lymphocyte in bonemarrow CD34+ cells Leu4+ T lymphocytes
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Haematology Parameters of Apparently Healthy Prospective Whole Blood Donors in a Nigerian Hospital Setting
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作者 Taiwo Modupe Balogun Kingsley Aile +2 位作者 Athanasius Chika Nnamani Olayinka Saidat Kareem Adenekan Salu 《Open Journal of Blood Diseases》 2023年第2期59-68,共10页
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
关键词 Whole Blood Donors Selection Haematology Parameters cd4 +ve T Lymphocyte Counts Nigeria
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Roles of microRNAs in immunopathogenesis of non-alcoholic fatty liver disease revealed by integrated analysis of microRNA and mRNA expression profiles 被引量:6
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作者 Yu-Jun Zhang Ying Hu +4 位作者 Jing Li Yu-Jing Chi Wei-Wei Jiang Feng Zhang Yu-Lan Liu 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2017年第1期65-79,共15页
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
关键词 microRNA-mRNA GUT non-alcoholic fatty liver disease cd4 T lymphocytes IMMUNOPATHOGENESIS
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Autoimmune pancreatitis characterized by predominant CD8+ Tlymphocyte infiltration 被引量:1
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作者 She-Yu Li Xiang-Yang Huang +2 位作者 Yong-Tao Chen Yi Liu Sha Zhao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第41期4635-4639,共5页
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
关键词 Autoimmune pancreatitis PANCREAS Pred-nisone CD8+ T and cd4 T lymphocytes CD20 Inflammatory cell INFILTRATION
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INVESTIGATION OF REGULATORY T CELLS IN PATIENTS WITH NON-SMALL CELL LUNG CANCER
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作者 张路 梁永杰 +3 位作者 任涛 朱辉 徐志龙 戴亚蕾 《Medical Bulletin of Shanghai Jiaotong University》 CAS 2010年第1期6-9,共4页
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
关键词 non-small cell lung cancer cd4 ^+ CD25^high regulatory T cells tumor-infiltrating lymphocyte
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A novel CD4+CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves’orbitopathy 被引量:4
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作者 Yue Wang Ziyi Chen +8 位作者 Tingjie Wang Hui Guo Yufeng Liu Ningxin Dang Shiqian Hu Liping Wu Chengsheng Zhang Kai Ye Bingyin Shi 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2021年第3期735-745,共11页
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
关键词 Graves'orbitopathy single-cell RNA sequencing cd4+cytotoxic T lymphocytes
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Stat5^(−/−)CD4^(+)T cells elicit anti-melanoma effect by CD4^(+)T cell remolding and Notch1 activation
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作者 Ke Jin Tong Li +7 位作者 Zhiyong Miao Jingjing Ran Luyu Chen Dachao Mou Chuang Wang Shasha Wu Hanshuo Yang Xin-Yuan Fu 《Science China(Life Sciences)》 SCIE CAS CSCD 2022年第9期1824-1839,共16页
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
关键词 STAT5 cd4^(+)tumor-infiltrating lymphocytes IFN-γ^(+)Th17 cell MELANOMA NOTCH1
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CD70 defines a subset of proinflammatory and CNSpathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis
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作者 Tessa Dhaeze Laurence Tremblay +15 位作者 Catherine Lachance Evelyn Peelen Stephanie Zandee Camille Grasmuck Lyne Bourbonnière Sandra Larouche Xavier Ayrignac Rose-Marie Rébillard Josée Poirier Boaz Lahav Pierre Duquette Marc Girard Robert Moumdjian Alain Bouthillier Catherine Larochelle Alexandre Prat 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2019年第7期652-665,共14页
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
关键词 CD70+cd4^(+)T lymphocytes multiple sclerosis CD27/CD70 pathway TGF-β1 TGF-Β3 soluble CD70 blood-brain barrier endothelial cells experimental autoimmune encephalitis TCR1640 transgene mouse model
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Effects of Xinfeng capsule on the Fas/FasL-mediated apoptotic pathway in patients with rheumatoid arthritis 被引量:9
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作者 Sun Yue Liu Jian Cao Yonghe 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2018年第4期601-609,共9页
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
关键词 ARTHRITIS RHEUMATOID Fas ligand protein cd4 lymphocyte count APOPTOSIS Xinfengcapsule
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Clinical outcomes and immune reconstitution in 103 advanced AIDS patients undergoing 12-month highly active antiretroviral therapy 被引量:6
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作者 DAI Yi QIU Zhi-feng LI Tai-sheng HAN Yang ZUO Ling-yan XIE Jing MA Xiao-jun LIU Zheng-yin WANG Ai-xia 《Chinese Medical Journal》 SCIE CAS CSCD 2006年第20期1677-1682,共6页
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
关键词 acquired immunodeficiency syndrome antiretroviral therapy highly active cd4 lymphocyte count immune reconstitution adverse effects
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Changes in peripheral blood inflammatory factors(TNF-α and IL-6) and intestinal flora in AIDS and HIV-positive individuals 被引量:15
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作者 Jing LU Sai-sai MA +1 位作者 Wei-ying ZHANG Jian-ping DUAN 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2019年第10期793-802,共10页
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
关键词 Acquired immune deficiency syndrome(AIDS) Tumor necrosis factor-α(TNF-α) Interleukin-6(IL-6) Intestinal flora cd4^+T lymphocytes
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