Journal article
Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells
The Journal of experimental medicine, v 204(1), pp 79-91
22 Jan 2007
PMID: 17190839
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The molecular events involved in the establishment and maintenance of CD4+ central memory and effector memory T cells (TCM and TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of CD4+ TCM depends, at least in part, on the activation and phosphorylation of signal transducer and activator of transcription 5a (STAT5a) and forkhead box O3a (FOXO3a). TCM showed a significant increase in the levels of phosphorylation of STAT5a compared with TEM in response to both IL-2 (P < 0.04) and IL-7 (P < 0.002); the latter is well known for its capacity to enhance T cell survival. Moreover, ex vivo TCM express higher levels of the transcriptionally inactive phosphorylated forms of FOXO3a and concomitantly lower levels of the proapoptotic FOXO3a target, Bim. Experiments aimed at blocking FOXO3a phosphorylation confirmed the role of this phosphoprotein in protecting TCM from apoptosis. Our results provide, for the first time in humans, an insight into molecular mechanisms that could be responsible for the longevity and persistence of CD4+ TCM.
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Details
- Title
- Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells
- Creators
- Catherine Riou - Hôpital Saint-LucBader Yassine-Diab - Hôpital Saint-LucJulien Van grevenynghe - Université de MontréalRoland Somogyi - Biosystemix, Ltd., Sydenham, Ontario K0H 2T0, CanadaLarry D. Greller - Biosystemix, Ltd., Sydenham, Ontario K0H 2T0, CanadaDominic Gagnon - Hôpital Saint-LucSylvain Gimmig - Hôpital Saint-LucPeter Wilkinson - Hôpital Saint-LucYu Shi - Hôpital Saint-LucMark J. Cameron - University Health NetworkRoberto Campos-Gonzalez - BD Biosciences (United States)Robert S. Balderas - BD Biosciences (United States)David Kelvin - University Health NetworkRafick-Pierre Sekaly - Hôpital Saint-LucElias K. Haddad - McGill University
- Publication Details
- The Journal of experimental medicine, v 204(1), pp 79-91
- Publisher
- Rockefeller University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000243753600013
- Scopus ID
- 2-s2.0-33846410668
- Other Identifier
- 991020099922504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental