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

TY - JOUR

T1 - Partial recovery of senescence and differentiation disturbances in CD8(+) T cell effector-memory cells in HIV-1 nfection after initiation of anti-retroviral treatment.

AU - Eberhard, Johanna Maria

AU - Ahmad, Fareed

AU - Hong, Henoch S

AU - Bhatnagar, Nupur

AU - Keudel, Phillip

AU - Schulze zur Wiesch, Julian

AU - Schmidt, Reinhold E

AU - Meyer-Olson, Dirk

N1 - © 2016 British Society for Immunology.

PY - 2016/11

Y1 - 2016/11

N2 - 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.

AB - 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.

U2 - 10.1111/cei.12837

DO - 10.1111/cei.12837

M3 - SCORING: Journal article

C2 - 27377704

VL - 186

SP - 227

EP - 238

JO - CLIN EXP IMMUNOL

JF - CLIN EXP IMMUNOL

SN - 0009-9104

IS - 2

ER -