Intrinsic role of FoxO3a in the development of CD8+ T Cell memory

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Journal titleJournal of Immunology
Pages10661075; # of pages: 10
Subjectactin; BIM protein; cytokine; lysosome associated membrane protein 1; protein Bid; PUMA protein; RAG1 protein; transcription factor FKHRL1; animal cell; animal experiment; animal model; antigen presentation; apoptosis; article; CD8+ T lymphocyte; cell expansion; cell survival; controlled study; cytokine release; degranulation; effector cell; female; listeriosis; lymphocyte function; memory T lymphocyte; mouse; nonhuman; pre T lymphocyte; priority journal; protein analysis; protein deficiency; protein expression; protein function; wild type; Animals; Antigen Presentation; Antigens, Bacterial; Apoptosis; Apoptosis Regulatory Proteins; CD8-Positive T-Lymphocytes; Cytokines; Cytotoxicity, Immunologic; Female; Forkhead Transcription Factors; Homeodomain Proteins; Immunologic Memory; L-Selectin; Listeria monocytogenes; Listeriosis; Lymphocyte Activation; Lymphocyte Subsets; Lymphokines; Lysosome-Associated Membrane Glycoproteins; Membrane Proteins; Mice; Mice, Inbred C57BL; Ovalbumin; Proto-Oncogene Proteins; Receptors, Interleukin-7; Tumor Suppressor Proteins
AbstractCD8+ 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. Copyright © 2013 by The American Association of Immunologists, Inc.
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AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269840
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Record identifier7abb551f-c5ff-42ba-8b21-d9f8088bf917
Record created2013-12-13
Record modified2016-05-09
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