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

Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.
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Wang C, Edilova MI, Wagar LE, Mujib S, Singer M, Bernard NF, Croughs T, Lederman MM, Sereti I, Fischl MA, Kremmer E, Ostrowski M, Routy JP, Watts TH,


Wang C, Edilova MI, Wagar LE, Mujib S, Singer M, Bernard NF, Croughs T, Lederman MM, Sereti I, Fischl MA, Kremmer E, Ostrowski M, Routy JP, Watts TH, (click to view)

Wang C, Edilova MI, Wagar LE, Mujib S, Singer M, Bernard NF, Croughs T, Lederman MM, Sereti I, Fischl MA, Kremmer E, Ostrowski M, Routy JP, Watts TH,

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Journal of immunology (Baltimore, Md. : 1950) 2017 12 08() pii 10.4049/jimmunol.1601254

Abstract

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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