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  • Title: Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice.
    Author: Nanno M, Kanari Y, Naito T, Inoue N, Hisamatsu T, Chinen H, Sugimoto K, Shimomura Y, Yamagishi H, Shiohara T, Ueha S, Matsushima K, Suematsu M, Mizoguchi A, Hibi T, Bhan AK, Ishikawa H.
    Journal: Gastroenterology; 2008 Feb; 134(2):481-90. PubMed ID: 18242214.
    Abstract:
    BACKGROUND & AIMS: T-cell receptor (TCR) gammadelta T cells are an important component of the mucosal immune system and regulate intestinal epithelial homeostasis. Interestingly, there is a significant increase in gammadelta T cells in the inflamed mucosa of patients with ulcerative colitis (UC). However, the role of gammadelta T cells in chronic colitis has not been fully identified. METHODS: TCRalpha-deficient mice, which spontaneously develop chronic colitis with many features of human UC including an increase in gammadelta T-cell population, represent an excellent model to investigate the role of gammadelta T cells in UC-like colitis. To identify the role of gammadelta T cells in this colitis, we herein have generated TCRgamma-deficient mice through deletion of all TCR Cgamma genes (Cgamma1, Cgamma2, Cgamma3, and Cgamma4) using the Cre/loxP site-specific recombination system and subsequently crossing these mice with TCRalpha-deficient mice. RESULTS: An increase in colonic gammadelta T cells was associated with the development of human UC as well as UC-like disease seen in TCRalpha-deficient mice. Interestingly, the newly established TCRalpha(-/-) x TCRgamma(-/-) double mutant mice developed significantly less severe colitis as compared with TCRalpha-deficient mice. The suppression of colitis in TCRalpha(-/-) x TCRgamma(-/-) double mutant mice was associated with a significant reduction of proinflammatory cytokine and chemokine productions and a decrease in neutrophil infiltration. CONCLUSIONS: gammadelta T cells are involved in the exacerbation of UC-like chronic disease. Therefore, gammadelta T cells may represent a promising therapeutic target for the treatment of human UC.
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