Immunosenescent CD57+CD4+ T-cells accumulate and contribute to interferon-γ responses in HIV patients responding stably to ART

Abstract

HIV-infected individuals responding to antiretroviral therapy (ART) after severe CD4+ T-cell depletion may retain low responses to recall antigens [eg: cytomegalovirus (CMV)] and altered expression of T-cell co-stimulatory molecules consistent with immunosenescence. We investigated the capacity of phenotypically senescent cells to generate cytokines in HIV patients receiving long-term ART (n = 18) and in healthy controls (n = 10). Memory T-cells were assessed by interferon (IFN)-γ ELISpot assay and flow cytometrically via IFN-γ or IL-2. Proportions of CD57(bright)CD28(null) CD4+ T-cells correlated with IFN-γ responses to CMV (p =0.009) and anti-CD3 (p =0.002) in HIV patients only. Proportions of CD57(bright)CD28(null) CD8+T-cells and CD8+ T-cell IFN-γ responses to CMV peptides correlated in controls but not HIV patients. IL-2 was predominantly produced by CD28+T-cells from all donors, whereas IFN-γ was mostly produced by CD57+ T-cells. The findings provide evidence of an accumulation of immunosenescent T-cells able to make IFN-γ. This may influence the pathogenesis of secondary viral infections in HIV patients receiving ART.