Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice

  • Nanno M
  • Kanari Y
  • Naito T
 et al. 
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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.

Author-supplied keywords

  • Animal
  • Animals
  • Antigen
  • Chronic Disease
  • Colitis/*genetics/*metabolism/pathology
  • Colon/metabolism/pathology
  • Disease Models
  • Homeostasis
  • Inbred C57BL
  • Intestinal Mucosa/metabolism/pathology
  • Knockout
  • Mice
  • Mutation/*genetics
  • Neutrophils/pathology
  • Receptors
  • Severity of Illness Index
  • Signal Transduction/physiology
  • T-Cell
  • T-Lymphocytes/*metabolism/pathology
  • alpha-beta/genetics/*m
  • gamma-delta/genetics/*
  • gd T

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Authors

  • M Nanno

  • Y Kanari

  • T Naito

  • N Inoue

  • T Hisamatsu

  • H Chinen

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