OBJECTIVE: To examine the effects of interferon-alpha (IFN-alpha) on T cell survival and activation in HIV infection. DESIGN: The effects of IFN-alpha 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-alpha. Percentages of apoptotic cells (positive for annexin V) and CD38 cells were determined among T cell subsets. RESULTS: IFN-alpha 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-alpha among CD4 cells from HIV-infected persons was not related to the percentages of activated (CD38 or CD45RO+CD38+) cells. Surprisingly, IFN-alpha 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-alpha was defined as CD28 negative, CD62 ligand (CD62L) intermediate/negative. CONCLUSIONS: Heightened expression of IFN-alpha 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.
OBJECTIVE: To examine the effects of interferon-alpha (IFN-alpha) on T cell survival and activation in HIV infection. DESIGN: The effects of IFN-alpha 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-infectedpersons and 17 healthy donors were incubated in vitro overnight with or without the addition of IFN-alpha. Percentages of apoptotic cells (positive for annexin V) and CD38 cells were determined among T cell subsets. RESULTS:IFN-alpha inhibited spontaneous apoptosis of CD4 and CD8 T lymphocytes. This protective activity was impaired in CD4 T cells from HIV-infectedpersons. The reduced protection of IFN-alpha among CD4 cells from HIV-infectedpersons was not related to the percentages of activated (CD38 or CD45RO+CD38+) cells. Surprisingly, IFN-alpha induced CD38 expression among CD8 T cells from HIV-infectedpersons, 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-alpha was defined as CD28 negative, CD62 ligand (CD62L) intermediate/negative. CONCLUSIONS: Heightened expression of IFN-alpha 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.
Authors: Adriano Boasso; Caroline M Royle; Spyridon Doumazos; Veronica N Aquino; Mara Biasin; Luca Piacentini; Barbara Tavano; Dietmar Fuchs; Francesco Mazzotta; Sergio Lo Caputo; Gene M Shearer; Mario Clerici; David R Graham Journal: Blood Date: 2011-09-19 Impact factor: 22.113
Authors: Joseph E Henriquez; Michael D Rizzo; Robert B Crawford; Peter Gulick; Norbert E Kaminski Journal: J Pharmacol Exp Ther Date: 2018-07-19 Impact factor: 4.030
Authors: Gareth A D Hardy; Scott F Sieg; Benigno Rodriguez; Wei Jiang; Robert Asaad; Michael M Lederman; Clifford V Harding Journal: Blood Date: 2009-03-19 Impact factor: 22.113