| T-cell intrinsic and extrinsic mechanisms of p27(Kip1) in the regulation of CD8 T-cell memory. | |
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MedLine Citation:
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PMID: 23207280 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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CD8 T cells exhibit dynamic alterations in proliferation and apoptosis during various phases of the CD8 T-cell response, but the mechanisms that regulate cellular proliferation from the standpoint of CD8 T-cell memory are not well defined. The cyclin-dependent kinase inhibitor p27(Kip1) functions as a negative regulator of the cell cycle in T cells, and it has been implicated in regulating cellular processes, including differentiation, transcription and migration. Here, we investigated whether p27(Kip1) regulates CD8 T-cell memory by T-cell-intrinsic or T-cell-extrinsic mechanisms, by conditional ablation of p27(Kip1) in T cells or non-T cells. Studies of T-cell responses to an acute viral infection show that p27(Kip1) negatively regulates the proliferation of CD8 T cells by T-cell-intrinsic mechanisms. However, the enhanced proliferation of CD8 T cells induced by T-cell-specific p27(Kip1) deficiency minimally affects the primary expansion or the magnitude of CD8 T-cell memory. Unexpectedly, p27(Kip1) ablation in non-T cells markedly augmented the number of high-quality memory CD8 T cells by enhancing the accumulation of memory precursor effector cells without increasing their proliferation. Further studies show that p27(Kip1) deficiency in immunizing dendritic cells fail to enhance CD8 T-cell memory. Nevertheless, we have delineated the T-cell-intrinsic, anti-proliferative activities of p27(Kip1) in CD8 T cells from its role as a factor in non-T cells that restricts the development of CD8 T-cell memory. These findings have implications in vaccine development and understanding the mechanisms that maintain T-cell homeostasis.Immunology and Cell Biology advance online publication, 4 December 2012; doi:10.1038/icb.2012.71. |
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Authors:
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Anna Jatzek; Melba Marie Tejera; Erin H Plisch; Matthew L Fero; M Suresh |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-04 |
Journal Detail:
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Title: Immunology and cell biology Volume: - ISSN: 1440-1711 ISO Abbreviation: Immunol. Cell Biol. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706300 Medline TA: Immunol Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, USA. |
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