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

BACKGROUND: 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 antiretroviral treatment (ART).

METHODS: 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 anti-retroviral therapy (ART) (n=20), were analyzed and compared to uninfected controls (n=25) by flow cytometry on bulk and HIV-specific MHC class I tetramer(+) CD8(+) T cells for expression of the memory markers CCR7, CD45RO, as well as the senescence marker CD57 and the differentiation and survival marker CD127. Furthermore, a subset of patients was longitudinally analyzed before and after initiation of ART.

RESULTS: Frequencies of CD57(+) CD8(+) T cells decreased after initiation of ART in central (Tcm) but not in effector memory (TemRO and TemRA) populations. 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 underrepresented in these patients. The frequency of the CD127(+) CD57(-) CD8(+) T cell subpopulation strongly correlated with absolute CD4(+) counts in HIV-infected patients before and after initiation of ART.

CONCLUSIONS: These findings can be interpreted as phenotypical correlate of CD8(+) memory T cell differentiation and the premature 'aging' of the immune system, which was even observed in successfully virally suppressed ART HIV patients. This article is protected by copyright. All rights reserved.