Transcription factor FOXO3a controls the persistence of memory CD4+ T cells during HIV infection View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-03

AUTHORS

Julien van Grevenynghe, Francesco A Procopio, Zhong He, Nicolas Chomont, Catherine Riou, Yuwei Zhang, Sylvain Gimmig, Genevieve Boucher, Peter Wilkinson, Yu Shi, Bader Yassine-Diab, Elias A Said, Lydie Trautmann, Mohamed El Far, Robert S Balderas, Mohamed-Rachid Boulassel, Jean-Pierre Routy, Elias K Haddad, Rafick-Pierre Sekaly

ABSTRACT

The persistence of central memory CD4(+) T cells (T(CM) cells) is a major correlate of immunological protection in HIV/AIDS, as the rate of T(CM) cell decline predicts HIV disease progression. In this study, we show that T(CM) cells and effector memory CD4(+) T cells (T(EM) cells) from HIV(+) elite controller (EC) subjects are less susceptible to Fas-mediated apoptosis and persist longer after multiple rounds of T cell receptor triggering when compared to T(CM) and T(EM) cells from aviremic successfully treated (ST) subjects or from HIV(-) donors. We show that persistence of T(CM) cells from EC subjects is a direct consequence of inactivation of the FOXO3a pathway. Silencing the transcriptionally active form of FOXO3a by small interfering RNA or by introducing a FOXO3a dominant-negative form (FOXO3a Nt) extended the long-term survival of T(CM) cells from ST subjects to a length of time similar to that of T(CM) cells from EC subjects. The crucial role of FOXO3a in the survival of memory cells will help shed light on the underlying immunological mechanisms that control viral replication in EC subjects. More... »

PAGES

266-274

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm1728

DOI

http://dx.doi.org/10.1038/nm1728

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004005456

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18311149


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