Mucosal T cells bearing TCRγδ play a protective role in intestinal inflammation

Kyoko Inagaki-Ohara, Takatoshi Chinen, Goro Matsuzaki, Atsuo Sasaki, Yukiko Sakamoto, Kenji Hiromatsu, Fukumi Nakamura-Uchiyama, Yukifumi Nawa, Akihiko Yoshimura

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Abstract

Intestinal intraepithelial lymphocytes (IEL) bearing TCRγδ represent a major T cell population in the murine intestine. However, the role of γδ IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we show that γδ IEL is an important protective T cell population against IBD. γδ T cell-deficient (Cδ-/-) mice developed spontaneous colitis with age and showed high susceptibility to Th1-type 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis at a young age. Transfer of γδ IEL to Cδ-/- mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-γ and TNF-α production and an increase of TGF-β production by IEL. Furthermore, a high level of IL-15, which inhibits activation-induced cell death to terminate inflammation, was expressed more in intestinal epithelial cells (EC) from TNBS-treated Cδ-/- mice than in those from wild-type mice. EC from wild-type mice significantly suppressed the IFN-γ production of IEL from TNBS-treated Cδ-/- mice, whereas EC from TNBS-treated Cδ-/- mice did not. These data indicate that γδ IEL play important roles in controlling IBD by regulating mucosal T cell activation cooperated with EC function. Our study suggests that enhancement of regulatory γδ T cell activity is a possible new cell therapy for colitis.

Original languageEnglish
Pages (from-to)1390-1398
Number of pages9
JournalJournal of Immunology
Volume173
Issue number2
Publication statusPublished - 2004 Jul 15

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Inagaki-Ohara, K., Chinen, T., Matsuzaki, G., Sasaki, A., Sakamoto, Y., Hiromatsu, K., Nakamura-Uchiyama, F., Nawa, Y., & Yoshimura, A. (2004). Mucosal T cells bearing TCRγδ play a protective role in intestinal inflammation. Journal of Immunology, 173(2), 1390-1398.