Objective To study the association between the expression of microRNA-155(miRNA-155)in peripheral blood CD4^+T lymphocytes and the level of semrn interferon-7(IFN-7)concentration and the severity of coronary artery di...Objective To study the association between the expression of microRNA-155(miRNA-155)in peripheral blood CD4^+T lymphocytes and the level of semrn interferon-7(IFN-7)concentration and the severity of coronary artery disease (CAD).Methods After coronary angiography,252patients with suspected unstable angina pectoris (UAP)were divided into the UAP group (128patients with CAD confirmed by angiography)and the control group (124patients without CAD confirmed by angiography).Fresh peripheral blood was extracted 16-24h before coronary angiography,CD4^+T lymphocytes was tested using immunomagnetic beads,the expression ofmiRNA-155was tested using quantitative PCR and the expression of IFN-7was tested using enzyme-linked immunosorbent assay (ELISA).According to the results of angiography,Gensini score of coronary artery lesions was analyzed.Furthermore,we also analysis the association between the level of miRNA-155in peripheral blood CD4^+T lymphocytes,the level of serum IFN-γand Gensini score of coronary lesion.Results The levels ofmiRNA-155(0.49±0.08vs.0.23±0.09)and IFN-7(227.58±26.01vs.141.23±17.89)in the UAP group were significantly higher than that of the control group,the difference was statistically significant.The level of miRNA-155and IFN-γwere positively correlated with Gensini score of CAD (r =0.534,r =0.713,respectively,all P <0.05).The level of miRNA-155was positively correlated with the level of IFN-γ,(r =0.686,P <0.05).Conclusions The level of miRNA-155in peripheral blood CD4^+T lymphocytes and the level of IFN-γ are closely correlated with the severity of CAD.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
AIM： To investigate the changes of lymphocyte subpopulations, especially CD4^＋CD25^ T regulatory cells in Smad3^-/- mice. METHODS： Hematological changes and changes of lymphocyte subpopulations were detected in Sm...AIM： To investigate the changes of lymphocyte subpopulations, especially CD4^＋CD25^ T regulatory cells in Smad3^-/- mice. METHODS： Hematological changes and changes of lymphocyte subpopulations were detected in Smad3＂/- mice using cell counter and flow cytometry, respectively, and compared to their littermate controls. RESULTS： The numbers of neutrophils and lymphocytes in peripheral blood were significantly increased in Smad3^-/- mice compared to littermate controls. CD19^＋ expressing cells in blood and spleen, and CD8^＋ T cells in thymus were all markedly decreased in Smad3^-/- mice. More important, Smad3^-/- mice had an increased population of CD4^＋CD25^＋ T cells in peripheral lymphoid tissues, including thymus, spleen, and lymph nodes. CONCLUSION： These observations suggest that the changes of lymphocyte subpopulations might play a role in susceptibility to inflammation of Smad3^-/- mice.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
Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the char...Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4^(+) programmed death 1 (PD-1)^(+)Foxp3^(−) T cells in relation to the B-cell response in patients with RA. Methods:This study included 155 patients with RA and 36 age- and sex-matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4^PD-1^(−)Foxp3^(+) T cells, including their proliferation, activation, cytokine production, and capacity to induce B-cell differentiation. Results:The proportion of CD4^(+)PD-1^(+)Foxp3^(−)T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p < 0.001), and this was positively associated with the B-cell response. Compared with CD4^PD-1 ^(+)Foxp3 ^(+) T cells, CD4^(+)PD-1^(+)Foxp3^(−)T cells from patients with RA exhibited increased expression of Ki67 ([6.52 ± 0.41]% vs. [3.87 ± 0.42]%, p < 0.01) and activation markers, produced higher levels of cytokines, and showed enhanced B-cell differentiation. Furthermore, anti-interleukin-6R antagonists decreased the proportion, activation, and cytokine production of CD4^(+)PD-1^(+)Foxp3^(−)T cells in vitro. The frequency of type 2 CD4^(+)PD-1^(+)Foxp3^(−)T cells was significantly higher in patients with RA than that in HCs ([37.27 ± 1.43]% vs. [29.05 ± 1.30]%, p < 0.05). Conclusions:Peripherally expanded CD4^(+)PD-1^(+)Foxp3^(−)T cells in patients with RA, which induced B-cell hyperactivity, may be inclined toward type 2 helper T cells. Our findings revealed a novel T-cell subset that contributes to B-cell hyperactivity in the pathogenesis of RA.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
Human immunodeficiency virus(HIV)has had an insightful impact about the state of healthiness of human immune system.Due to great improvement in drug therapy,HIV infections have been reduced by 17%over the past eight y...Human immunodeficiency virus(HIV)has had an insightful impact about the state of healthiness of human immune system.Due to great improvement in drug therapy,HIV infections have been reduced by 17%over the past eight years.It has been proved that most effective treatment HAART(Highly Active Anti Retroviral Therapy)mainly controls the diseases progression but it does not eradicate the diseases completely.Reverse Transcriptase Inhibitor drugs specially associated with virus specific Cytotoxic T-Lymphocyte(CTL)that declines with disease progression. CTL responses against AIDS pathogenesis could be potential in the dynamics of virus replication, recognition and clearance of infected cells.In this research article a mathematical model has been proposed on the basis of CTL response suppression in the chronic phase of infection due to presence of virus.We also consider the growth of the virus population from the infected CD4^+T cells budding process and from the other infected cells like macrophages and thymocytes.Our analytical and numerical studies are consistent with existing observations from allied areas.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
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
Meigs’syndrome(MS),a rare complication of benign ovarian tumors,is easily misdiagnosed as ovarian cancer(OC).We retrospectively reviewed the clinical laboratory data of patients diagnosed with MS from 2009 to 2018.Se...Meigs’syndrome(MS),a rare complication of benign ovarian tumors,is easily misdiagnosed as ovarian cancer(OC).We retrospectively reviewed the clinical laboratory data of patients diagnosed with MS from 2009 to 2018.Serum carbohydrate antigen 125 and HE4 levels were higher in the MS group than in the ovarian thecoma-fibroma(OTF)and healthy control groups(all P<0.05).However,the serum HE4 levels were lower in the MS group than in the OC group(P<0.001).A routine blood test showed that the absolute counts and percentages of lymphocytes were significantly lower in the MS group than in the OTF and control groups(all P<0.05).However,these variables were higher in the MS group than in the OC group(both P<0.05).The neutrophil-to-lymphocyte ratio(NLR)was also significantly lower,whereas the lymphocyte-to-monocyte ratio was higher in the MS group than in the OC group(both P<0.05).The NLR,platelet-to-lymphocyte ratio,and systemic immune index were significantly higher in the MS group than in the OTF and control groups(all P<0.05).The hypoxia-inducible factor-1 mRNA levels were also significantly higher,whereas the glucose transporter 1,lactate dehydrogenase,and enolase 1 mRNA levels were lower in peripheral CD4+T cells obtained preoperatively in a patient with MS than those in patients with OTF,patients with OC,and controls(all P<0.05).The expression of these four glucose metabolism genes was preferentially restored to normal levels after the tumor resection of MS(P<0.001).These clinical laboratory features can be useful in improving the preoperative diagnostic accuracy of MS.展开更多
文摘Objective To study the association between the expression of microRNA-155(miRNA-155)in peripheral blood CD4^+T lymphocytes and the level of semrn interferon-7(IFN-7)concentration and the severity of coronary artery disease (CAD).Methods After coronary angiography,252patients with suspected unstable angina pectoris (UAP)were divided into the UAP group (128patients with CAD confirmed by angiography)and the control group (124patients without CAD confirmed by angiography).Fresh peripheral blood was extracted 16-24h before coronary angiography,CD4^+T lymphocytes was tested using immunomagnetic beads,the expression ofmiRNA-155was tested using quantitative PCR and the expression of IFN-7was tested using enzyme-linked immunosorbent assay (ELISA).According to the results of angiography,Gensini score of coronary artery lesions was analyzed.Furthermore,we also analysis the association between the level of miRNA-155in peripheral blood CD4^+T lymphocytes,the level of serum IFN-γand Gensini score of coronary lesion.Results The levels ofmiRNA-155(0.49±0.08vs.0.23±0.09)and IFN-7(227.58±26.01vs.141.23±17.89)in the UAP group were significantly higher than that of the control group,the difference was statistically significant.The level of miRNA-155and IFN-γwere positively correlated with Gensini score of CAD (r =0.534,r =0.713,respectively,all P <0.05).The level of miRNA-155was positively correlated with the level of IFN-γ,(r =0.686,P <0.05).Conclusions The level of miRNA-155in peripheral blood CD4^+T lymphocytes and the level of IFN-γ are closely correlated with the severity of CAD.
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AIM： To investigate the changes of lymphocyte subpopulations, especially CD4^＋CD25^ T regulatory cells in Smad3^-/- mice. METHODS： Hematological changes and changes of lymphocyte subpopulations were detected in Smad3＂/- mice using cell counter and flow cytometry, respectively, and compared to their littermate controls. RESULTS： The numbers of neutrophils and lymphocytes in peripheral blood were significantly increased in Smad3^-/- mice compared to littermate controls. CD19^＋ expressing cells in blood and spleen, and CD8^＋ T cells in thymus were all markedly decreased in Smad3^-/- mice. More important, Smad3^-/- mice had an increased population of CD4^＋CD25^＋ T cells in peripheral lymphoid tissues, including thymus, spleen, and lymph nodes. CONCLUSION： These observations suggest that the changes of lymphocyte subpopulations might play a role in susceptibility to inflammation of Smad3^-/- mice.
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.
基金National Natural Science Foundation of China,Grant/Award Numbers:82071834,82271839,82302047Doctoral Start-up Foundation of Liaoning Province,Grant/Award Numbers:2023−BS-160Dalian Medical University Interdisciplinary Research Cooperation Project Team Funding,Grant/Award Numbers:JCHZ2023010.
文摘Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4^(+) programmed death 1 (PD-1)^(+)Foxp3^(−) T cells in relation to the B-cell response in patients with RA. Methods:This study included 155 patients with RA and 36 age- and sex-matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4^PD-1^(−)Foxp3^(+) T cells, including their proliferation, activation, cytokine production, and capacity to induce B-cell differentiation. Results:The proportion of CD4^(+)PD-1^(+)Foxp3^(−)T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p < 0.001), and this was positively associated with the B-cell response. Compared with CD4^PD-1 ^(+)Foxp3 ^(+) T cells, CD4^(+)PD-1^(+)Foxp3^(−)T cells from patients with RA exhibited increased expression of Ki67 ([6.52 ± 0.41]% vs. [3.87 ± 0.42]%, p < 0.01) and activation markers, produced higher levels of cytokines, and showed enhanced B-cell differentiation. Furthermore, anti-interleukin-6R antagonists decreased the proportion, activation, and cytokine production of CD4^(+)PD-1^(+)Foxp3^(−)T cells in vitro. The frequency of type 2 CD4^(+)PD-1^(+)Foxp3^(−)T cells was significantly higher in patients with RA than that in HCs ([37.27 ± 1.43]% vs. [29.05 ± 1.30]%, p < 0.05). Conclusions:Peripherally expanded CD4^(+)PD-1^(+)Foxp3^(−)T cells in patients with RA, which induced B-cell hyperactivity, may be inclined toward type 2 helper T cells. Our findings revealed a novel T-cell subset that contributes to B-cell hyperactivity in the pathogenesis of RA.
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Research is supported by the Government of India,Ministry of Science and Technology,Mathematical Science office,No.SR/S4/MS:558/08
文摘Human immunodeficiency virus(HIV)has had an insightful impact about the state of healthiness of human immune system.Due to great improvement in drug therapy,HIV infections have been reduced by 17%over the past eight years.It has been proved that most effective treatment HAART(Highly Active Anti Retroviral Therapy)mainly controls the diseases progression but it does not eradicate the diseases completely.Reverse Transcriptase Inhibitor drugs specially associated with virus specific Cytotoxic T-Lymphocyte(CTL)that declines with disease progression. CTL responses against AIDS pathogenesis could be potential in the dynamics of virus replication, recognition and clearance of infected cells.In this research article a mathematical model has been proposed on the basis of CTL response suppression in the chronic phase of infection due to presence of virus.We also consider the growth of the virus population from the infected CD4^+T cells budding process and from the other infected cells like macrophages and thymocytes.Our analytical and numerical studies are consistent with existing observations from allied areas.
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.
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.
基金supported by the National Natural Science Foundation of China(No.81772779)“Professionals from SixPronged Top-Talent Program”of Jiangsu Province(No.LGY2017068)+2 种基金“The Six Top Talent Project”of Jiangsu Province(No.2015-WSN-034)Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province(No.ZDRCA2016003)Key Laboratory for Medicine of Jiangsu Province of China(No.ZDXKB2016005).
文摘Meigs’syndrome(MS),a rare complication of benign ovarian tumors,is easily misdiagnosed as ovarian cancer(OC).We retrospectively reviewed the clinical laboratory data of patients diagnosed with MS from 2009 to 2018.Serum carbohydrate antigen 125 and HE4 levels were higher in the MS group than in the ovarian thecoma-fibroma(OTF)and healthy control groups(all P<0.05).However,the serum HE4 levels were lower in the MS group than in the OC group(P<0.001).A routine blood test showed that the absolute counts and percentages of lymphocytes were significantly lower in the MS group than in the OTF and control groups(all P<0.05).However,these variables were higher in the MS group than in the OC group(both P<0.05).The neutrophil-to-lymphocyte ratio(NLR)was also significantly lower,whereas the lymphocyte-to-monocyte ratio was higher in the MS group than in the OC group(both P<0.05).The NLR,platelet-to-lymphocyte ratio,and systemic immune index were significantly higher in the MS group than in the OTF and control groups(all P<0.05).The hypoxia-inducible factor-1 mRNA levels were also significantly higher,whereas the glucose transporter 1,lactate dehydrogenase,and enolase 1 mRNA levels were lower in peripheral CD4+T cells obtained preoperatively in a patient with MS than those in patients with OTF,patients with OC,and controls(all P<0.05).The expression of these four glucose metabolism genes was preferentially restored to normal levels after the tumor resection of MS(P<0.001).These clinical laboratory features can be useful in improving the preoperative diagnostic accuracy of MS.
