Homeostatic proliferation of naive CD4+ T cells in mesenteric lymph nodes generates gut-tropic Th17 cells

Takeshi Kawabe, Shu Lan Sun, Tsuyoshi Fujita, Satoshi Yamaki, Atsuko Asao, Takeshi Takahashi, Takanori So, Naoto Ishii

研究成果: Article査読

27 被引用数 (Scopus)

抄録

Homeostatic proliferation of naive T cells in the spleen and cutaneous lymph nodes supplies memory-phenotype T cells. The "systemic" proliferative responses divide distinctly into fast or slow cell division rates. 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, "gut-specific" 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 α4β7 + 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 α4β7+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.

本文言語English
ページ(範囲)5788-5798
ページ数11
ジャーナルJournal of Immunology
190
11
DOI
出版ステータスPublished - 2013 6 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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