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

2 Citations (Scopus)

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

Fingerprint

TNF Receptor-Associated Factor 1
Ribosomal Protein S6
Interleukin-7
HIV
T-Lymphocytes
Therapeutics
Lymphocytic Choriomeningitis
Viruses
CD4 Lymphocyte Count
HIV Infections
Phosphotransferases
Cell Count

ASJC Scopus subject areas

  • Immunology

Cite this

Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy. / Wang, Chao; Edilova, Maria I.; Wagar, Lisa E.; Mujib, Shariq; Singer, Meromit; Bernard, Nicole F.; Croughs, Thérèse; Lederman, Michael M.; Sereti, Irini; Fischl, Margaret A; Kremmer, Elisabeth; Ostrowski, Mario; Routy, Jean Pierre; Watts, Tania H.

In: Journal of Immunology, Vol. 200, No. 2, 15.01.2018, p. 558-564.

Research output: Contribution to journalArticle

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 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, vol. 200, no. 2, pp. 558-564. https://doi.org/10.4049/jimmunol.1601254
Wang, Chao ; Edilova, Maria I. ; Wagar, Lisa E. ; Mujib, Shariq ; Singer, Meromit ; Bernard, Nicole F. ; Croughs, Thérèse ; Lederman, Michael M. ; Sereti, Irini ; Fischl, Margaret A ; Kremmer, Elisabeth ; Ostrowski, Mario ; Routy, Jean Pierre ; Watts, Tania H. / Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy. In: Journal of Immunology. 2018 ; Vol. 200, No. 2. pp. 558-564.
@article{250ec787d12a4d06a45350ae4db81cd8,
title = "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.",
author = "Chao Wang and Edilova, {Maria I.} and Wagar, {Lisa E.} and Shariq Mujib and Meromit Singer and Bernard, {Nicole F.} and Th{\'e}r{\`e}se Croughs and Lederman, {Michael M.} and Irini Sereti and Fischl, {Margaret A} and Elisabeth Kremmer and Mario Ostrowski and Routy, {Jean Pierre} and Watts, {Tania H.}",
year = "2018",
month = "1",
day = "15",
doi = "10.4049/jimmunol.1601254",
language = "English (US)",
volume = "200",
pages = "558--564",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy

AU - Wang, Chao

AU - Edilova, Maria I.

AU - Wagar, Lisa E.

AU - Mujib, Shariq

AU - Singer, Meromit

AU - Bernard, Nicole F.

AU - Croughs, Thérèse

AU - Lederman, Michael M.

AU - Sereti, Irini

AU - Fischl, Margaret A

AU - Kremmer, Elisabeth

AU - Ostrowski, Mario

AU - Routy, Jean Pierre

AU - Watts, Tania H.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85044724421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044724421&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1601254

DO - 10.4049/jimmunol.1601254

M3 - Article

VL - 200

SP - 558

EP - 564

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -