TY - JOUR
T1 - Homeostatic proliferation of naive CD4+ T cells in mesenteric lymph nodes generates gut-tropic Th17 cells
AU - Kawabe, Takeshi
AU - Sun, Shu Lan
AU - Fujita, Tsuyoshi
AU - Yamaki, Satoshi
AU - Asao, Atsuko
AU - Takahashi, Takeshi
AU - So, Takanori
AU - Ishii, Naoto
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878077227&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1203111
DO - 10.4049/jimmunol.1203111
M3 - 学術論文
C2 - 23610141
AN - SCOPUS:84878077227
SN - 0022-1767
VL - 190
SP - 5788
EP - 5798
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -