Dynamics and consequences of IL-21 production in HIV-infected individuals: A longitudinal and cross-sectional study

Alexandre Iannello, Mohamed Rachid Boulassel, Suzanne Samarani, Olfa Debbeche, Cécile Tremblay, Emil Toma, Jean Pierre Routy, Ali Ahmad

Research output: Contribution to journalArticle

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Abstract

IL-21 is a relatively newly discovered immune-enhancing cytokine that plays an essential role in controlling chronic viral infections. It is produced mainly by CD4+ T cells, which are also the main targets of HIV-1 and are often depleted in HIV-infected individuals. Therefore, we sought to determine the dynamics of IL-21 production and its potential consequences for the survival of CD4+ T cells and frequencies of HIV-specific CTL. For this purpose, we conducted a series of cross-sectional and longitudinal studies on different groups of HIV-infected patients and show in this study that the cytokine production is compromised early in the course of the infection. The serum cytokine concentrations correlate with CD4+ T cell counts in the infected persons. Among different groups of HIV-infected individuals, only elite controllers maintain normal production of the cytokine. Highly active antiretroviral therapy only partially restores the production of this cytokine. Interestingly, HIV infection of human CD4+ T cells inhibits cytokine production by decreasing the expression of c-Maf in virus-infected cells, not in uninfected bystander cells. We also show that the frequencies of IL-21-producing HIV-specific, but not human CMV-specific, Ag-experienced CD4+ T cells are decreased in HIV-infected viremic patients. Furthermore, we demonstrate in this study that recombinant human IL-21 prevents enhanced spontaneous ex vivo death of CD4+ T cells from HIV-infected patients. Together, our results suggest that serum IL-21 concentrations may serve as a useful biomarker for monitoring HIV disease progression and the cytokine may be considered for immunotherapy in HIV-infected patients.

Original languageEnglish
Pages (from-to)114-126
Number of pages13
JournalJournal of Immunology
Volume184
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

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Cross-Sectional Studies
HIV
Cytokines
T-Lymphocytes
interleukin-21
Highly Active Antiretroviral Therapy
Virus Diseases
CD4 Lymphocyte Count
Serum
Immunotherapy
HIV Infections
Longitudinal Studies
Disease Progression
HIV-1
Biomarkers
Viruses
Survival
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Dynamics and consequences of IL-21 production in HIV-infected individuals : A longitudinal and cross-sectional study. / Iannello, Alexandre; Boulassel, Mohamed Rachid; Samarani, Suzanne; Debbeche, Olfa; Tremblay, Cécile; Toma, Emil; Routy, Jean Pierre; Ahmad, Ali.

In: Journal of Immunology, Vol. 184, No. 1, 01.01.2010, p. 114-126.

Research output: Contribution to journalArticle

Iannello, Alexandre ; Boulassel, Mohamed Rachid ; Samarani, Suzanne ; Debbeche, Olfa ; Tremblay, Cécile ; Toma, Emil ; Routy, Jean Pierre ; Ahmad, Ali. / Dynamics and consequences of IL-21 production in HIV-infected individuals : A longitudinal and cross-sectional study. In: Journal of Immunology. 2010 ; Vol. 184, No. 1. pp. 114-126.
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