Immunosenescent CD57⁺CD4⁺T-cells Accumulate and Contribute to Interferon-γResponses in HIV Patients Responding Stably to ART

Abstract

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). 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.

Neutrophils in antiretroviral therapy–controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment

“…20 As expected, 21,22 ART-treated HIV-infected patients had higher percentages of CD38 1 HLA-DR 1 (activation markers) and CD57 1 (immunosenescence marker) CD8 and CD4 memory T cells than did HCs (see Fig E2, A and B, in this article's Online Repository at www.jacionline.org). Percentages of CD57 1 CD8 and CD4 memory T cells correlated with percentages of the corresponding CD38 1 HLA-DR 1 CD8 and CD4 memory T cells (see Fig E2, C).…”

High Numbers of Differentiated Effector CD4 T Cells Are Found in Patients with Cancer and Correlate with Clinical Response after Neoadjuvant Therapy of Breast Cancer

“…were observed in other chronic antigen stimulations, without complete characterization of their phenotype or effector functions (30)(31)(32)(33)(34)(35). The chCD4s present in patients with cancer are probably related to these previously described subsets.…”

“…Indeed, these features have been observed in diseases in which chronic antigen stimulation is obvious, such as HIV infection (27,29,30), or hypothesized, such as rheumatoid arthritis and multiple sclerosis (31)(32)(33)(34)(35). In mUMs, CD28 expression was low on effector chCD4s (Fig.…”

“…In contrast, CD57, a marker associated with immunosenescence and chronic antigen stimulation (30,34,36), but also expressed by germinal center (GC) helper T cells (37,38) was highly expressed only on a fraction of the effector chCD4s, suggesting some heterogeneity of this subset. However, the expression of PD1 an inhibitory receptor found on chronically stimulated CD4 T cells and on GC CD4 T cells, and whose expression often parallels CD57 (39) was heterogeneous and not correlated with CD57 expression in mUMs (Fig.…”

DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia

“…This profile was further implemented by the preserved ability of ICL T cells to secrete interferon-g and by the absence of upregulation of exhaustion markers. 41,48,49 Thus, patients with ICL may encounter an accelerated T-cell senescence, rather than exhaustion.…”