The proportion of CD57+ cells among effector CD8+ T cells is lower in HIV controllers compared with antiretroviral therapy-treated patients

Abstract

Background: HIV infection has often been linked to faster immune ageing. We sought to determine whether or not treatment-naive spontaneous HIV-1 controllers (HICs) and ART-exposed patients differ with regard to the expression of cell senescence markers.Methods:Eighty-eight chronically infected HICs and ART-exposed patients (median time since infection: 15 years) with an undetectable plasma HIV RNA load (at least for the previous 2 years) were included. We used flow cytometry to measure immunosenescence markers (KLRG-1 and CD57) expression in fresh blood samples collected from patients and healthy donors.Results:For the CD8+ T-cell population as a whole, the ART-exposed but not the HIC patients exhibited a much higher proportion of KLRG-1+ and CD57+ CD8+ T cells than healthy blood donors. For the CD8+ T-cell subsets, HICs had a lower proportion of CD57+ effector CD8+ T cells than ART patients or healthy blood donors, whereas the proportions of KLRG-1+ effector were similar. A similar trend was observed for terminal effectors. No impact of age, sex or standard parameters of infection (CD4+ percentage, protective HLA allele, viral blips) was observed. The difference in the proportion of CD57+ cells between HICs and ART was observed more specifically in long-term infected patients (>20 years). However, whenever considering the CD57- effector memory and effector subsets, the cytotoxic granule content was greater in HICs than in ART.Conclusion:The proportion of CD57+ effector CD8+ T cells is lower in HICs than in ART-exposed patients. This profile may be beneficial by ensuring limited senescence associated with consistent cytotoxic potential.