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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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1 Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
2 Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada
3 Broad Institute, Cambridge, MA 02142
4 Chronic Viral Illness Service, Division of Clinical Immunology, Research Institute, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada
5 Agence Nationale de Recherches sur le SIDA, 75013 Paris, France
6 Center for AIDS Research, Case Western Reserve University School of Medicine, Cleveland, OH 44106
7 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
8 Miami Center for AIDS Research, University of Miami School of Medicine, Miami, FL 33136
9 Helmholtz Zentrum Munchen, German Research Centre for Environmental Health, 81377 Munich, Germany
10 Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, Ontario M5B1W8, Canada
11 Division of Hematology and Immunodeficiency Service, McGill University, Montreal, Quebec H3A 1A3, Canada