Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drug...Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drugs. Ethanol is reward drug and a CNS depressant especially at high doses. The study determined the effect of sustained heavy ethanol drinking by HIV-infected patients on d4T/3TC/NVP regimen on CD4+ cell counts in Uganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A case control study using repeated measures design with serial measurements model was used. The patients on stavudine (d4T) 30 mg, lamivudine (3TC) 150 mg and nevirapine (NVP) 200 mg and chronic alcohol use were recruited. A total of 41 patients (20 in alcohol group and 21 in control group) were screened for chronic alcohol use by WHO AUDIT tool and chronic alcohol use biomarkers. They were followed up for 9 months with blood sampling done at 3 months intervals. CD4+ cell count was determined using Facscalibur Flow Cytometer system. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ ALT ratio). Data were analysed using SAS 2003 version 9.1 statistical package with repeated measures fixed model and the means were compared using student t-test. The mean CD4+ cell counts in all the groups were lower than the reference ranges at baseline and gradually increased at 3, 6 and 9 months of follow-up. The mean CD4+ cell counts were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p > 0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV-infected patients on d4T/3TC/NVP treatment regimen.展开更多
Background:The pathogenesis of multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE-an animal model of MS)is primarily mediated by T cells.However,recent studies have only focused on interleukin(IL)...Background:The pathogenesis of multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE-an animal model of MS)is primarily mediated by T cells.However,recent studies have only focused on interleukin(IL)-17-secreting CD4^(+)T-helper cells,also known as Th17 cells.This study aimed to compare Th17 cells and IL-17-secreting CD8^(+)T-cytotoxic cells(Tc17)in the context of MS/EAE.Methods:Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptides 35-55(MOG35-55),pertussis toxin,and complete Freund's adjuvant to establish the EAE animal model.T cells were isolated from the spleen(12-14 days postimmunization).CD4^(+)and CD8^(+)T cells were purified using isolation kit and then differentiated into Th17 and Tc17,respectively,using MOG35-55 and IL-23.The secretion levels of interferon-(IFN-γ)and IL-17 were measured via enzyme-linked immunosorbent assay using cultured CD4^(+)and CD8^(+)T cell supernatants.The pathogenicity of Tc17 and Th17 cells was assessed through adoptive transfer(tEAE),with the clinical course assessed using an EAE score(0-5).Hematoxylin and eosin as well as Luxol fast blue staining were used to examine the spinal cord.Purified CD8^(+)CD3^(+)and CD4^(+)CD3^(+)cells differentiated into Tc17 and Th17 cells,respectively,were stimulated with MOG35-55 peptide for proliferation assays.Results:The results showed that Tc17 cells(15,951±19855VS.55,709±4196cpm;p<0.050)exhibited a weaker response to highest dose(20μg/mL)MOG35-55 than Th17 cells.However,this response was not dependent on Th17 cells.After the 48h stimulation,at the highest dose(20μg/mL)of MOG35-55.Tc17 cells secreted lower levels of IFN-(280.00±15.00vs.556.67±15.28pg/mL,p<0.050)and IL-17(102.67±5.86 pg/mL vs.288.33±12.58 pg/mL;p<0.050)than Th17 cells.Similar patterns were observed for IFN-γsecretion at 96 and 144h.Furthermore,Tc17 cell-induced tEAE mice exhibited similar EAE scores to Th17 cell-induced tEAE mice and also showed similar inflammation and demyelination.Conclusion:The degree of pathogenicity of Tc17 cells in EAE is lower than that of Th17 cells.Future investigation on different immune cells and EAE models is warranted to determine the mechanisms underlying MS.展开更多
文摘Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drugs. Ethanol is reward drug and a CNS depressant especially at high doses. The study determined the effect of sustained heavy ethanol drinking by HIV-infected patients on d4T/3TC/NVP regimen on CD4+ cell counts in Uganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A case control study using repeated measures design with serial measurements model was used. The patients on stavudine (d4T) 30 mg, lamivudine (3TC) 150 mg and nevirapine (NVP) 200 mg and chronic alcohol use were recruited. A total of 41 patients (20 in alcohol group and 21 in control group) were screened for chronic alcohol use by WHO AUDIT tool and chronic alcohol use biomarkers. They were followed up for 9 months with blood sampling done at 3 months intervals. CD4+ cell count was determined using Facscalibur Flow Cytometer system. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ ALT ratio). Data were analysed using SAS 2003 version 9.1 statistical package with repeated measures fixed model and the means were compared using student t-test. The mean CD4+ cell counts in all the groups were lower than the reference ranges at baseline and gradually increased at 3, 6 and 9 months of follow-up. The mean CD4+ cell counts were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p > 0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV-infected patients on d4T/3TC/NVP treatment regimen.
基金Scientific Research Project of Hunan Provincial Health Commission,Grant/Award Number:C2023030765University-Hospital Joint-Fund of Hunan University of Chinese Medicine,Grant/Award Number:2022XYLH198+2 种基金Key Plans of Hunan Administration Traditional Chinese Medicine,Grant/Award Number:A2023039Technology Plan Project of Zhuzhou City,Hunan Province,Grant/Award Number:2021-009Fund for Creative Research Group of Affiliated First Hospital of Hunan Traditional Chinese Medical College,Grant/Award Number:2021 B-003。
文摘Background:The pathogenesis of multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE-an animal model of MS)is primarily mediated by T cells.However,recent studies have only focused on interleukin(IL)-17-secreting CD4^(+)T-helper cells,also known as Th17 cells.This study aimed to compare Th17 cells and IL-17-secreting CD8^(+)T-cytotoxic cells(Tc17)in the context of MS/EAE.Methods:Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptides 35-55(MOG35-55),pertussis toxin,and complete Freund's adjuvant to establish the EAE animal model.T cells were isolated from the spleen(12-14 days postimmunization).CD4^(+)and CD8^(+)T cells were purified using isolation kit and then differentiated into Th17 and Tc17,respectively,using MOG35-55 and IL-23.The secretion levels of interferon-(IFN-γ)and IL-17 were measured via enzyme-linked immunosorbent assay using cultured CD4^(+)and CD8^(+)T cell supernatants.The pathogenicity of Tc17 and Th17 cells was assessed through adoptive transfer(tEAE),with the clinical course assessed using an EAE score(0-5).Hematoxylin and eosin as well as Luxol fast blue staining were used to examine the spinal cord.Purified CD8^(+)CD3^(+)and CD4^(+)CD3^(+)cells differentiated into Tc17 and Th17 cells,respectively,were stimulated with MOG35-55 peptide for proliferation assays.Results:The results showed that Tc17 cells(15,951±19855VS.55,709±4196cpm;p<0.050)exhibited a weaker response to highest dose(20μg/mL)MOG35-55 than Th17 cells.However,this response was not dependent on Th17 cells.After the 48h stimulation,at the highest dose(20μg/mL)of MOG35-55.Tc17 cells secreted lower levels of IFN-(280.00±15.00vs.556.67±15.28pg/mL,p<0.050)and IL-17(102.67±5.86 pg/mL vs.288.33±12.58 pg/mL;p<0.050)than Th17 cells.Similar patterns were observed for IFN-γsecretion at 96 and 144h.Furthermore,Tc17 cell-induced tEAE mice exhibited similar EAE scores to Th17 cell-induced tEAE mice and also showed similar inflammation and demyelination.Conclusion:The degree of pathogenicity of Tc17 cells in EAE is lower than that of Th17 cells.Future investigation on different immune cells and EAE models is warranted to determine the mechanisms underlying MS.
