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

Chao Wang, Maria I. Edilova, Lisa E. Wagar, Shariq Mujib, Meromit Singer, Nicole F. Bernard, Thérèse Croughs, Michael M. Lederman, Irini Sereti, Margaret A Fischl, Elisabeth Kremmer, Mario Ostrowski, Jean Pierre Routy, Tania H. Watts

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)558-564
Number of pages7
JournalJournal of Immunology
Volume200
Issue number2
DOIs
StatePublished - Jan 15 2018

ASJC Scopus subject areas

  • Immunology

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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., Routy, J. P., & Watts, T. H. (2018). Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy. Journal of Immunology, 200(2), 558-564. https://doi.org/10.4049/jimmunol.1601254