Journal article
Intrinsic Role of FoxO3a in the Development of CD8(+) T Cell Memory
The Journal of immunology (1950), v 190(3), pp 1066-1075
01 Feb 2013
PMID: 23277488
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
CD8(+) T cells undergo rapid expansion during infection with intracellular pathogens, which is followed by swift and massive culling of primed CD8(+) T cells. The mechanisms that govern the massive contraction and maintenance of primed CD8(+) T cells are not clear. We show in this study that the transcription factor, FoxO3a, does not influence Ag presentation and the consequent expansion of CD8(+) T cell response during Listeria monocytogenes infection, but plays a key role in the maintenance of memory CD8(+) T cells. The effector function of primed CD8(+) T cells as revealed by cytokine secretion and CD107a degranulation was not influenced by inactivation of FoxO3a. Interestingly, FoxO3a-deficient CD8(+) T cells displayed reduced expression of proapoptotic molecules BIM and PUMA during the various phases of response, and underwent reduced apoptosis in comparison with wild-type cells. A higher number of memory precursor effector cells and memory subsets was detectable in FoxO3a-deficient mice compared with wild-type mice. Furthermore, FoxO3a-deficient memory CD8(+) T cells upon transfer into normal or RAG1-deficient mice displayed enhanced survival. These results suggest that FoxO3a acts in a cell-intrinsic manner to regulate the survival of primed CD8(+) T cells. The Journal of Immunology, 2013, 190: 1066-1075.
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Details
- Title
- Intrinsic Role of FoxO3a in the Development of CD8(+) T Cell Memory
- Creators
- Fanny Tzelepis - Institute for Biological SciencesJulie Joseph - University of OttawaElias K. Haddad - Gene (China)Susanne MacLean - Institute for Biological SciencesRenu Dudani - Institute for Biological SciencesFabien Agenes - Université de MontréalStanford L. Peng - Virginia Mason Medical CenterRafick-Pierre Sekaly - Virginia Mason Medical CenterSubash Sad - University of Ottawa
- Publication Details
- The Journal of immunology (1950), v 190(3), pp 1066-1075
- Publisher
- American Association of Immunologists
- Number of pages
- 10
- Grant note
- Foreign Affairs and International Trade Canada DP1DA028871 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000313784200025
- Scopus ID
- 2-s2.0-84872701318
- Other Identifier
- 991020099858504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology