Immunosenescent CD57+CD4+T-cells Accumulate and Contribute to Interferon-γResponses 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)-γELISpot assay and flow cytometrically via IFN-γor IL-2. Proportions of CD57brightCD28nullCD4+T-cells correlated with IFN-γresponses to CMV (p= 0.009) and anti-CD3 (p= 0.002) in HIV patients only. Proportions of CD57brightCD28nullCD8+T-cells and CD8+T-cell IFN-γresponses to CMV peptides correlated in controls but not HIV patients. IL-2 was predominantly produced by CD28+T-cells from all donors, whereas IFN-γwas 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.