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Article
Nature Medicine 14, 266 - 274 (2008)
Published online: 2 March 2008 | doi:10.1038/nm1728
Transcription factor FOXO3a controls the persistence of memory CD4+ T cells during HIV infection
Julien van Grevenynghe1,2,3, Francesco A Procopio1,2,3, Zhong He1,2,3, Nicolas Chomont1,2,3, Catherine Riou1, Yuwei Zhang1,2,3, Sylvain Gimmig1, Genevieve Boucher1, Peter Wilkinson1, Yu Shi1,2,3, Bader Yassine-Diab1,2,3, Elias A Said1,2,3, Lydie Trautmann1,2,3, Mohamed El Far1,2,3, Robert S Balderas4, Mohamed-Rachid Boulassel5, Jean-Pierre Routy3,5, Elias K Haddad1,2,3,6,7 & Rafick-Pierre Sekaly1,2,3,6,7
Abstract
The persistence of central memory CD4+ T cells (TCM cells) is a major correlate of immunological protection in HIV/AIDS, as the rate of TCM cell decline predicts HIV disease progression. In this study, we show that TCM cells and effector memory CD4+ T cells (TEM 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 TCM and TEM cells from aviremic successfully treated (ST) subjects or from HIV- donors. We show that persistence of TCM 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 TCM cells from ST subjects to a length of time similar to that of TCM 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.
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