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^brightCD28^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^brightCD28^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.

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