The CD4+CD25+regulatory T lymphocytes have been implicated in suppressing T cell immune responses. Our aim was to characterize the frequency, phenotype, function, and specificity of CD4+CD25 +T cells in hepatitis C vi...The CD4+CD25+regulatory T lymphocytes have been implicated in suppressing T cell immune responses. Our aim was to characterize the frequency, phenotype, function, and specificity of CD4+CD25 +T cells in hepatitis C virus (HCV)infection. Peripheral CD4 +CD25+cells from recovered (n = 15), chronic infected (n = 30), and normal control (n = 15) subjects were analyzed ex vivo for quantitation, phenotype, and effect on HCV specific Interferon gamma production and proliferation, CD4+CD25+specificity was determined by intracellular cytokine staining for interleukin 10 (IL-10). A higher proportion of CD4+CD25+were found in chronic infection (mean, 3.02%) when compared with recovered (1.64%, P = .001) and normal controls (2.27%, P = .02). CD4+CD25+cells display CD45RO high, CD45RA low,CD28 high, CD62L high,and CD95 high phenotype. HCV specific interferon gamma activity was enhanced in peripheral blood mononuclear cells depleted of CD4+CD25+and suppressed in peripheral blood mononuclear cells enriched with CD4+CD25+. Depletion of CD4 +CD25+cells also enhanced HCV specific CD4+and CD8+T cell proliferation. Cytokine analysis suggested CD4 +CD25+cells secrete transforming growth factor beta (TGF-β1) and IL-10. The inhibitory role for TGF-β1 was confirmed by anti TGF β1. Transwell studies showed CD4+CD25+mediated suppression to be dose dependent and requiring cell contact. CD4+CD25+cells showed HCV specificity through IL-10 production, with a frequency ranging from 1.9%to 5.3%. A positive correlation was detected between CD4 +CD25+T cell frequency and HCV RNA titer, whereas an inverse relation was found with liver inflammatory activity. In conclusion, CD4+CD25+T lymphocytes constitute a highly differentiated population and appear to play a role in viral persistence by suppressing HCV specific T cell responses in a cell cell contact manner.展开更多
文摘The CD4+CD25+regulatory T lymphocytes have been implicated in suppressing T cell immune responses. Our aim was to characterize the frequency, phenotype, function, and specificity of CD4+CD25 +T cells in hepatitis C virus (HCV)infection. Peripheral CD4 +CD25+cells from recovered (n = 15), chronic infected (n = 30), and normal control (n = 15) subjects were analyzed ex vivo for quantitation, phenotype, and effect on HCV specific Interferon gamma production and proliferation, CD4+CD25+specificity was determined by intracellular cytokine staining for interleukin 10 (IL-10). A higher proportion of CD4+CD25+were found in chronic infection (mean, 3.02%) when compared with recovered (1.64%, P = .001) and normal controls (2.27%, P = .02). CD4+CD25+cells display CD45RO high, CD45RA low,CD28 high, CD62L high,and CD95 high phenotype. HCV specific interferon gamma activity was enhanced in peripheral blood mononuclear cells depleted of CD4+CD25+and suppressed in peripheral blood mononuclear cells enriched with CD4+CD25+. Depletion of CD4 +CD25+cells also enhanced HCV specific CD4+and CD8+T cell proliferation. Cytokine analysis suggested CD4 +CD25+cells secrete transforming growth factor beta (TGF-β1) and IL-10. The inhibitory role for TGF-β1 was confirmed by anti TGF β1. Transwell studies showed CD4+CD25+mediated suppression to be dose dependent and requiring cell contact. CD4+CD25+cells showed HCV specificity through IL-10 production, with a frequency ranging from 1.9%to 5.3%. A positive correlation was detected between CD4 +CD25+T cell frequency and HCV RNA titer, whereas an inverse relation was found with liver inflammatory activity. In conclusion, CD4+CD25+T lymphocytes constitute a highly differentiated population and appear to play a role in viral persistence by suppressing HCV specific T cell responses in a cell cell contact manner.
