Interferon-α differentially rescues CD4 and CD8 T cells from apoptosis in HIV infection

Abstract

Objective: To examine the effects of interferon-α (IFN-α) on T cell survival and activation in HIV infection. Design: The effects of IFN-α on spontaneous apoptosis and CD38 expression among T cell subsets were determined in vitro and studied in relation to CD4 cell counts, plasma HIV RNA levels and the age of the subjects. Methods: Peripheral blood mononuclear cells from 48 HIV-infected persons and 17 healthy donors were incubated in vitro overnight with or without the addition of IFN-α. Percentages of apoptotic cells (positive for annexin V) and CD38 cells were determined among T cell subsets. Results: IFN-α inhibited spontaneous apoptosis of CD4 and CD8 T lymphocytes. This protective activity was impaired in CD4 T cells from HIV-infected persons. The reduced protection of IFN-α among CD4 cells from HIV-infected persons was not related to the percentages of activated (CD38 or CD45RO+CD38+) cells. Surprisingly, IFN-α induced CD38 expression among CD8 T cells from HIV-infected persons, and the magnitude of this effect was directly related to circulating CD4 T cell count. The CD8 T cell subset that expressed CD38 in response to IFN-α was defined as CD28 negative, CD62 ligand (CD62L) intermediate/negative. Conclusions: Heightened expression of IFN-α in HIV infection may contribute to the phenotypic activation state that characterizes chronic infection while a diminished responsiveness of CD4 T cells to the protective effect of this cytokine may contribute to differential survival of CD4 and CD8 T cells in HIV disease.