Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of anti-retroviral treatment. (23rd August 2016)

• Record Type: Journal Article
• Authors: Eberhard, J M; Ahmad, F; Hong, H S; Bhatnagar, N; Keudel, P; Schulze zur Wiesch, J; Schmidt, R E; Meyer-Olson, D
• Is Part Of: Clinical and experimental immunology. Volume 186:Number 2(2016:Nov.)
• Page Start: 227
• Page End: 238
• Publication Date: 2016-08-23
• Subjects: AIDS -- cytotoxic T cells -- T cells -- viral; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12837
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: 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. Graphical Abstract: