title: 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.
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany. j.eberhard@uke.de.|Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. j.eberhard@uke.de.
authors.forename: J M
authors.initials: JM
authors.lastname: Eberhard
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.|Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.|Unit of Cytokines and Inflammation, Institute Pasteur, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Bhatnagar
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Keudel
authors.affiliation: Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.|DZIF German Center for Infection-Partner Sites Hamburg, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schulze Zur Wiesch
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.|DZIF German Center for Infection-Partner Sites Hamburg, Hannover, Germany.
authors.forename: R E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Meyer-Olson
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D018655:Lymphocyte Count
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte
keywords: AIDS; T cells; cytotoxic T cells; viral