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Wang, C.* ; Edilova, M.I.* ; Wagar, L.E.* ; Mujib, S.* ; Singer, M.* ; Bernard, N.F.* ; Croughs, T.* ; Lederman, M.M.* ; Sereti, I.* ; Fischl, M.A.* ; Kremmer, E. ; Ostrowski, M.A.* ; Routy, J.P.* ; Watts, T.H.*

Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.

J. Immunol. 200, 558-564 (2018)
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Open Access Green as soon as Postprint is submitted to ZB.
Copyright © 2018 by The American Association of Immunologists, Inc. IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice. Previous results showed that IL-7 can restore TRAF1 expression in virus-specific CD8 T cells in mice, rendering them sensitive to anti-4-1BB agonist therapy. In this article, we show that IL-7 therapy in humans increases the number of circulating HIV-specific CD8 T cells. For a subset of patients, we also observed an increased frequency of TRAF1+HIV-specific CD8 T cells 10 wk after completion of IL-7 treatment. IL-7 treatment increased levels of phospho-ribosomal protein S6 in HIV-specific CD8 T cells, suggesting increased activation of the metabolic checkpoint kinase mTORC1. Thus, IL-7 therapy in antiretroviral therapy-treated patients induces sustained changes in the number and phenotype of HIV-specific T cells.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Recombinant Human Interleukin-7; Chronic Viral-infection; Bim Modulation; In-vivo; Survival; Mtor; Differentiation; Phosphorylation; Persistence; Multicenter
Language
Publication Year 2018
Prepublished in Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Journal Journal of Immunology
Quellenangaben Volume: 200, Issue: 2, Pages: 558-564 Article Number: , Supplement: ,
Publisher American Association of Immunologists
Publishing Place Bethesda
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501760-001
DOI 10.4049/jimmunol.1601254
WOS ID WOS:000419443900021
Scopus ID 85044724421
PubMed ID 29222166
Erfassungsdatum 2017-12-27
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