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
Authors
Keywords
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.

Year of Publication
2018
Journal
J Immunol
Volume
200
Issue
2
Pages
558-564
Date Published
2018 01 15
ISSN
1550-6606
DOI
10.4049/jimmunol.1601254
PubMed ID
29222166
PubMed Central ID
PMC5760332
Links
Grant list
UM1 AI069501 / AI / NIAID NIH HHS / United States
Z01 AI001082-01 / Intramural NIH HHS / United States
THA-11906 / CIHR / Canada
FDN 143250 / CIHR / Canada
U01 AI069501 / AI / NIAID NIH HHS / United States
MOP-74492 / CIHR / Canada
P30 AI036219 / AI / NIAID NIH HHS / United States
103230 / CIHR / Canada