@article{82ce0695780f41c288d370f0359fa777,
title = "Transcription factor FOXO3a controls the persistence of memory CD4 + T cells during HIV infection",
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 T EM 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.",
author = "{Van Grevenynghe}, Julien and Procopio, {Francesco A.} and Zhong He and Nicolas Chomont and Catherine Riou and Yuwei Zhang and Sylvain Gimmig and Genevieve Boucher and Peter Wilkinson and Yu Shi and Bader Yassine-Diab and Said, {Elias A.} and Lydie Trautmann and Far, {Mohamed El} and Balderas, {Robert S.} and Boulassel, {Mohamed Rachid} and Routy, {Jean Pierre} and Haddad, {Elias K.} and Sekaly, {Rafick Pierre}",
note = "Funding Information: HIV+ subjects We selected ten subjects chronically infected with HIV and undergoing HAART treatment rendering them aviremic, called here ST subjects. We also included five EC donors who had been evaluated with a very stringent set of inclusion criteria in this study. This research was approved by the Office of Research Ethics, Royal Victoria Hospital, McGill University Health Center, and by the Comit{\'e} d{\textquoteright}{\'E}thique de la Recherche, Centre Hospitalier de l{\textquoteright}Universite de Montr{\'e}al. The virological and immunological profiles for all HIV+ subjects are summarized in Supplementary Figure 1. Funding Information: We thank D. Trono (University of Geneva) for the lentiviral vector pWPI, packaging plasmid psPAX2 and envelope plasmid pMD2G. We thank M. Lainesse and Y. Chouikh for expert technical assistance. We thank L. Greller and R. Somogyi for statistical assistance. We also want to thank all study participants. J.v.G. is a recipient of the Fond de la Recherche M{\'e}dicale fellowship, L.T. and Funding Information: E.A.S. are funded by the Canadian Institutes of Health Research and N.C. is supported by The American Foundation for AIDS Research (fellowship number 106634-38-RFRL). This study was supported by funds from the National Institutes of Health, the Canadian Institutes of Health Research, Genome Quebec, Genome Canada, Fonds de Recherche en Sant{\'e} du Quebec and the Canadian Network for Vaccines and Immunotherapeutics. R.-P.S. is the Canada Research Chair in Human Immunology. J.-P.R., is a clinician-scientist supported by Fonds de Recherche en Sant{\'e} du Quebec. We thank R. Seder, M. Lederman, Q. Eichbaum and P. Ancuta for critically reviewing the manuscript. We would also like to thank the members of the Cleveland Immunopathogenesis Consortium for helpful discussions.",
year = "2008",
month = mar,
doi = "10.1038/nm1728",
language = "English (US)",
volume = "14",
pages = "266--274",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "3",
}