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The cyclin\u2010dependent kinase inhibitor p27<jats:sup>Kip1<\/jats:sup> 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<jats:sup>Kip1<\/jats:sup> regulates CD8 T\u2010cell memory by T\u2010cell\u2010intrinsic or T\u2010cell\u2010extrinsic mechanisms, by conditional ablation of p27<jats:sup>Kip1<\/jats:sup> in T cells or non\u2010T cells. Studies of T\u2010cell responses to an acute viral infection show that p27<jats:sup>Kip1<\/jats:sup> negatively regulates the proliferation of CD8 T cells by T\u2010cell\u2010intrinsic mechanisms. However, the enhanced proliferation of CD8 T cells induced by T\u2010cell\u2010specific p27<jats:sup>Kip1<\/jats:sup> deficiency minimally affects the primary expansion or the magnitude of CD8 T\u2010cell memory. Unexpectedly, p27<jats:sup>Kip1<\/jats:sup> ablation in non\u2010T cells markedly augmented the number of high\u2010quality memory CD8 T cells by enhancing the accumulation of memory precursor effector cells without increasing their proliferation. Further studies show that p27<jats:sup>Kip1<\/jats:sup> deficiency in immunizing dendritic cells fail to enhance CD8 T\u2010cell memory. Nevertheless, we have delineated the T\u2010cell\u2010intrinsic, anti\u2010proliferative activities of p27<jats:sup>Kip1<\/jats:sup> in CD8 T cells from its role as a factor in non\u2010T cells that restricts the development of CD8 T\u2010cell memory. These findings have implications in vaccine development and understanding the mechanisms that maintain T\u2010cell homeostasis.<\/jats:p>","DOI":"10.1038\/icb.2012.71","type":"journal-article","created":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T10:40:49Z","timestamp":1354617649000},"page":"120-129","source":"Crossref","is-referenced-by-count":13,"title":["T\u2010cell intrinsic and extrinsic mechanisms of p27<sup>Kip1<\/sup> in the regulation of CD8 T\u2010cell memory"],"prefix":"10.1111","volume":"91","author":[{"given":"Anna","family":"Jatzek","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2010Madison Madison USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melba","family":"Marie Tejera","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2010Madison Madison USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin 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