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

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.

• Authors: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 200 Issue 2 Pg. 558-564 (01 15 2018) ISSN: 1550-6606 [Electronic] United States
• PMID: 29222166 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 by The American Association of Immunologists, Inc.

Chemical References

• Cytokines
• HAVCR2 protein, human
• Hepatitis A Virus Cellular Receptor 2
• Interleukin-7
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Recombinant Proteins
• Ribosomal Protein S6
• TNF Receptor-Associated Factor 1
• Mechanistic Target of Rapamycin Complex 1

Topics

• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cytokines (biosynthesis)
• Gene Expression
• HIV Infections (drug therapy, immunology, metabolism, virology)
• HIV-1 (immunology)
• Hepatitis A Virus Cellular Receptor 2 (metabolism)
• Humans
• Interleukin-7 (pharmacology, therapeutic use)
• Lymphocyte Count
• Mechanistic Target of Rapamycin Complex 1 (metabolism)
• Programmed Cell Death 1 Receptor (metabolism)
• Protein Binding
• Recombinant Proteins (pharmacology, therapeutic use)
• Ribosomal Protein S6 (genetics, metabolism)
• TNF Receptor-Associated Factor 1 (genetics, metabolism)
• Viral Load