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Hepatitis C virus (HCV) becomes persistent in the majority of infected individuals. In doing so, the virus evades host adaptive immune responses, although the mechanisms responsible in this evasion are not clear. Several groups have demonstrated weak or absent HCV-specific CD4+T cell responses during chronic HCV infection using proliferation assays and, more recently, class II tetramers. However, the functional status of HCV-specific CD4+T cells in resolved and persistent infection is poorly understood. Using interferon γ(IFN-γ) and interleukin 2 (IL-2) enzyme-linked immunospot assays, we analyzed cytokine secretion patterns in chronically infected patients and compared them with those with resolved infection. In the spontaneous resolver group, strong IL-2 secretion in relation to IFN-γsecretion was observed. However, in the persistently infected group, a consistent and significant loss of IL-2-secreting cells, compared with IFN-γ-secreting cells, was identified. In vitro addition of IL-2 had a substantial effect in restoring CD4+T cell activity. In conclusion, failure of IL-2 secretion, as opposed to physical deletion or complete functional unresponsiveness, appears to be an important determinant of the status of CD4+T cell populations in chronic HCV infection. Loss of IL-2 secretory capacity may lead to disruption of IFN-γand proliferative function in vivo-a status that characterizes the cellular immune response in both CD4+and CD8+compartments in chronic disease.
Several agents have demonstrated that the virus evades host adaptive immune responses, although the mechanisms responsible in this evasion are not clear. Several groups have demonstrated in weak or the majority of infected individuals. T cell responses during chronic HCV infection using proliferation assays and, more recently, class II tetramers. However, the functional status of HCV-specific CD4 + T cells in resolved and persistent infections is poorly understood. Using interferon γ (IFN- γ) and interleukin 2 (IL-2) enzyme-linked immunospot assays, we analyzed cytokine secretion patterns in chronically infected patients and compared them with those with resolved infection. In the spontaneous resolver group, strong IL-2 secretion in relation to IFN-γ secretion was observed However, in the persistently infected group, a consistent and significant loss of IL-2-secreting cells, compared with IFN-γ-secreting cells, was identified. of conclusion that the IL-2 had a substantial effect in restoring CD4 + T cell activity. In conclusion, failure of IL-2 secretion, as opposed to physical deletion or complete functional unresponsiveness, appears to be an important determinant of the status of CD4 + T cell populations in chronic HCV infection. Loss of IL-2 secretory capacity may lead to disruption of IFN-γ and proliferative function in vivo-a status that characterizes the cellular immune response in both CD4 + and CD8 + compartments in chronic disease.