TY - JOUR
T1 - Intestinal lamina propria retaining CD4+CD25+ regulatory T cells is a suppressive site of intestinal inflammation
AU - Makita, Shin
AU - Kanai, Takanori
AU - Nemoto, Yasuhiro
AU - Totsuka, Teruji
AU - Okamoto, Ryuichi
AU - Tsuchiya, Kiichiro
AU - Yamamoto, Masafumi
AU - Kiyono, Hiroshi
AU - Watanabe, Mamoru
PY - 2007/4/15
Y1 - 2007/4/15
N2 - It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only does active suppression by regulatory T (TREG) cells play an important role in the normal intestinal homeostasis, but also that its dysregulation of immune response leads to the development of inflammatory bowel disease. In this study, we demonstrate that murine CD4+CD25+ T cells residing in the intestinal lamina propria (LP) constitutively express CTLA-4, glucocorticoid-induced TNFR, and Foxp3 and suppress proliferation of responder CD4+ T cells in vitro. Furthermore, cotransfer of intestinal LP CD4+CD25+ T cells prevents the development of chronic colitis induced by adoptive transfer of CD4+CD45RBhigh T cells into SCID mice. When lymphotoxin (LT)α-deficient intercrossed Rag2 double knockout mice (LTα-/- × Rag2-/-), which lack mesenteric lymph nodes and Peyer's patches, are transferred with CD4+CD45RB high T cells, they develop severe wasting disease and chronic colitis despite the delayed kinetics as compared with the control LTα +/+ × Rag2-/- mice transferred with CD4 +CD45RBhigh T cells. Of note, when a mixture of splenic CD4+CD25+ TREG cells and CD4 +CD45RBhigh T cells are transferred into LTα-/- × Rag2-/- recipients, CD4 +CD25+ TREG cells migrate into the colon and prevent the development of colitis in LTα-/- × Rag2 -/- recipients as well as in the control LTα+/+ × Rag2-/- recipients. These results suggest that the intestinal LP harboring CD4+CD25+ TREG cells contributes to the intestinal immune suppression.
AB - It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only does active suppression by regulatory T (TREG) cells play an important role in the normal intestinal homeostasis, but also that its dysregulation of immune response leads to the development of inflammatory bowel disease. In this study, we demonstrate that murine CD4+CD25+ T cells residing in the intestinal lamina propria (LP) constitutively express CTLA-4, glucocorticoid-induced TNFR, and Foxp3 and suppress proliferation of responder CD4+ T cells in vitro. Furthermore, cotransfer of intestinal LP CD4+CD25+ T cells prevents the development of chronic colitis induced by adoptive transfer of CD4+CD45RBhigh T cells into SCID mice. When lymphotoxin (LT)α-deficient intercrossed Rag2 double knockout mice (LTα-/- × Rag2-/-), which lack mesenteric lymph nodes and Peyer's patches, are transferred with CD4+CD45RB high T cells, they develop severe wasting disease and chronic colitis despite the delayed kinetics as compared with the control LTα +/+ × Rag2-/- mice transferred with CD4 +CD45RBhigh T cells. Of note, when a mixture of splenic CD4+CD25+ TREG cells and CD4 +CD45RBhigh T cells are transferred into LTα-/- × Rag2-/- recipients, CD4 +CD25+ TREG cells migrate into the colon and prevent the development of colitis in LTα-/- × Rag2 -/- recipients as well as in the control LTα+/+ × Rag2-/- recipients. These results suggest that the intestinal LP harboring CD4+CD25+ TREG cells contributes to the intestinal immune suppression.
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U2 - 10.4049/jimmunol.178.8.4937
DO - 10.4049/jimmunol.178.8.4937
M3 - Article
C2 - 17404275
AN - SCOPUS:34247160955
VL - 178
SP - 4937
EP - 4946
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -