Intestinal lamina propria retaining CD4+CD25+ regulatory T cells is a suppressive site of intestinal inflammation

Shin Makita, Takanori Kanai, Yasuhiro Nemoto, Teruji Totsuka, Ryuichi Okamoto, Kiichiro Tsuchiya, Masafumi Yamamoto, Hiroshi Kiyono, Mamoru Watanabe

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4937-4946
Number of pages10
JournalJournal of Immunology
Volume178
Issue number8
DOIs
Publication statusPublished - 2007 Apr 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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