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The fast proliferation is critical for generation of effector memory T cells. Because effector memory T cells are abundant in the lamina propria of the intestinal tissue, \u201cgut-specific\u201d homeostatic proliferation of naive T cells may be important for generation of intestinal effector memory T cells. However, such organ-specific homeostatic proliferation of naive T cells has not yet been addressed. In this study, we examined the gut-specific homeostatic proliferation by transferring CFSE-labeled naive CD4+ T cells into sublethally irradiated mice and separately evaluating donor cell division and differentiation in the intestine, mesenteric lymph nodes (MLNs), and other lymphoid organs. We found that the fast-proliferating cell population in the intestine and MLNs had a gut-tropic \u03b14\u03b27+ Th17 phenotype and that their production was dependent on the presence of commensal bacteria and OX40 costimulation. Mesenteric lymphadenectomy significantly reduced the Th17 cell population in the host intestine. Furthermore, FTY720 treatment induced the accumulation of \u03b14\u03b27+IL-17A+ fast-dividing cells in MLNs and eliminated donor cells in the intestine, suggesting that MLNs rather than intestinal tissues are essential for generating intestinal Th17 cells. These results reveal that MLNs play a central role in inducing gut-tropic Th17 cells and in maintaining CD4+ T cell homeostasis in the small intestine.<\/jats:p>","DOI":"10.4049\/jimmunol.1203111","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T04:31:16Z","timestamp":1366691476000},"page":"5788-5798","source":"Crossref","is-referenced-by-count":46,"title":["Homeostatic Proliferation of Naive CD4+ T Cells in Mesenteric Lymph Nodes Generates Gut-Tropic Th17 Cells"],"prefix":"10.1093","volume":"190","author":[{"given":"Takeshi","family":"Kawabe","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-lan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yamaki","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Asao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]},{"name":"Central Institute for Experimental Animals , Kawasaki 210-0821,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"So","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,6,1]]},"reference":[{"key":"2025032407040027400_r1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.272.5258.60","article-title":"Lymphocyte homing and homeostasis","volume":"272","author":"Butcher","year":"1996","journal-title":"Science"},{"key":"2025032407040027400_r2","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.immuni.2008.11.002","article-title":"Homeostasis of naive and memory T cells","volume":"29","author":"Surh","year":"2008","journal-title":"Immunity"},{"key":"2025032407040027400_r3","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nri2657","article-title":"Naive T cell homeostasis: from awareness of space to a sense of place","volume":"9","author":"Takada","year":"2009","journal-title":"Nat. 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