Logo image
Back
Inflammatory Cytokines Drive CD4(+) T-Cell Cycling and Impaired Responsiveness to Interleukin 7: Implications for Immune Failure in HIV Disease
Journal article   Open access   Peer reviewed

Inflammatory Cytokines Drive CD4(+) T-Cell Cycling and Impaired Responsiveness to Interleukin 7: Implications for Immune Failure in HIV Disease

Carey L. Shive, Joseph C. Mudd, Nicholas T. Funderburg, Scott F. Sieg, Benjamin Kyi, Doug A. Bazdar, Davide Mangioni, Andrea Gori, Jeffrey M. Jacobson, Ari D. Brooks, …
The Journal of infectious diseases, v 210(4), pp 619-629
15 Aug 2014
DOI: https://doi.org/10.1093/infdis/jiu125
PMID: 24585897
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://academic.oup.com/jid/article-pdf/210/4/619/18070005/jiu125.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1093/infdis/jiu125View
Published, Version of Record (VoR) Open

Abstract

Immunology Infectious Diseases Life Sciences & Biomedicine Microbiology Science & Technology
Background. Systemic inflammation has been linked to a failure to normalize CD4(+) T-cell numbers in treated human immunodeficiency virus (HIV) infection. Although inflammatory cytokines such as interleukin 6 (IL-6) are predictors of disease progression in treated HIV infection, it is not clear how or whether inflammatory mediators contribute to immune restoration failure. Methods. We examined the in vitro effects of IL-6 and interleukin 1 beta (IL-1 beta) on peripheral blood T-cell cycling and CD127 surface expression. Results. The proinflammatory cytokine IL-1 beta induces cell cycling and turnover of memory CD4(+) T cells, and IL-6 can induce low-level cycling of naive T cells. Both IL-1 beta and IL-6 can decrease T-cell surface expression and RNA levels of CD127, the interleukin 7 receptor alpha chain (IL-7R alpha). Preexposure of healthy peripheral blood mononuclear cells (PBMCs) to IL-6 or IL-1 beta attenuates IL-7-induced Stat5 phosphorylation and induction of the prosurvival factor Bcl-2 and the gut homing integrin alpha 4 beta 7. We found elevated expression of IL-1 beta in the lymphoid tissues of patients with HIV infection that did not normalize with antiretroviral therapy. Conclusions. Induction of CD4(+) T-cell turnover and diminished T-cell responsiveness to IL-7 by IL-1 beta and IL-6 exposure may contribute to the lack of CD4(+) T-cell reconstitution in treated HIV-infected subjects.

Metrics

6 Record Views
66 citations in Web of Science
72 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Industry collaboration
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Infectious Diseases
Microbiology
Logo image