| DOI | Resolve DOI: https://doi.org/10.4049/jimmunol.1200639 |
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| Author | Search for: Tzelepis, F.1; Search for: Joseph, J.1; Search for: Haddad, E.K.1; Search for: MacLean, S.1; Search for: Dudani, R.; Search for: Agenes, F.; Search for: Peng, S.L.; Search for: Sekaly, R.-P.; Search for: Sad, S.1 |
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| Affiliation | - National Research Council of Canada. NRC Institute for Biological Sciences
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| Format | Text, Article |
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| Subject | actin; 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; CD8+ T lymphocyte; cell expansion; cell survival; cytokine release; degranulation; effector cell; female; listeriosis; lymphocyte function; memory T lymphocyte; mouse; pre T lymphocyte; protein analysis; protein deficiency; protein expression; protein function; wild type; 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 |
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| 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. Copyright © 2013 by The American Association of Immunologists, Inc. |
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| Publication date | 2013 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 21269840 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 7abb551f-c5ff-42ba-8b21-d9f8088bf917 |
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| Record created | 2013-12-13 |
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| Record modified | 2020-04-22 |
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