Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of anti-retroviral treatment

Abstract

Immune senescence as well as disturbed CD8⁺ T cell differentiation are a hallmark of chronic HIV infection. Here, we investigated to what extent immune senescence is reversible after initiation of anti-retroviral treatment (ART). Peripheral blood mononuclear cells (PBMCs) from a cohort of HIV patients with different disease courses, including untreated viral controllers (n = 10), viral non-controllers (n = 16) and patients on ART (n = 20), were analysed and compared to uninfected controls (n = 25) by flow cytometry on bulk and HIV-specific major histocompatibility complex (MHC) class I tetramer⁺ CD8⁺ T cells for expression of the memory markers CCR7 and CD45RO, as well as the senescence marker CD57 and the differentiation and survival marker CD127. Furthermore, a subset of patients was analysed longitudinally before and after initiation of ART. Frequencies of CD57⁺ CD8⁺ T cells decreased after initiation of ART in central memory (Tcm) but not in effector memory T cell populations (TemRO and TemRA). The frequency of CD127⁺ CD8⁺ cells increased in Tcm and TemRO. We observed a reduction of CD127^- T cells in Tcm, TemRO and partially in TemRA subsets after initiation of ART. Importantly, HIV-specific CD8⁺ TemRO cells predominantly displayed a CD127^- CD57⁺ phenotype in untreated HIV-patients, whereas the CD127⁺ CD57^- phenotype was under-represented in these patients. The frequency of the CD127⁺ CD57^- CD8⁺ T cell subpopulation correlated strongly with absolute CD4⁺ counts in HIV-infected patients before and after initiation of ART. These findings can be interpreted as a phenotypical correlate of CD8⁺ memory T cell differentiation and the premature 'ageing' of the immune system, which was even observed in successfully virally suppressed HIV patients.

Keywords: AIDS; T cells; cytotoxic T cells; viral.