title: Mucosal T cells bearing TCRgammadelta play a protective role in intestinal inflammation.
abstract: Intestinal intraepithelial lymphocytes (IEL) bearing TCRgammadelta represent a major T cell population in the murine intestine. However, the role of gammadelta IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we show that gammadelta IEL is an important protective T cell population against IBD. gammadelta T cell-deficient (Cdelta(-/-)) 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 gammadelta IEL to Cdelta(-/-) mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-gamma and TNF-alpha production and an increase of TGF-beta 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 Cdelta(-/-) mice than in those from wild-type mice. EC from wild-type mice significantly suppressed the IFN-gamma production of IEL from TNBS-treated Cdelta(-/-) mice, whereas EC from TNBS-treated Cdelta(-/-) mice did not. These data indicate that gammadelta IEL play important roles in controlling IBD by regulating mucosal T cell activation cooperated with EC function. Our study suggests that enhancement of regulatory gammadelta T cell activity is a possible new cell therapy for colitis.
authors.affiliation: Department of Infectious Diseases, Division of Parasitic Disease, University of Miyazaki, Miyazaki Medical College, Kiyotake, Miyazaki, Japan. INAGAKI@med.miyazaki-u.ac.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Inagaki-Ohara
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Chinen
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Sasaki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Hiromatsu
authors.forename: Fukumi
authors.initials: F
authors.lastname: Nakamura-Uchiyama
authors.forename: Yukifumi
authors.initials: Y
authors.lastname: Nawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell