Enhanced Formation of Azoxymethane‐induced Colorectal Adenocarcinoma in γδ T Lymphocyte‐deficient Mice

T cell receptor (TCR) γδ ‐positive T lymphocytes, which are localized mostly within the intraepithe‐lial space of intestinal epithelium, have been suggested to play a role in maintaining the normal configuration of intestinal epithelium. However, the role of TCRγδ ‐positive T lymphocytes in the formation and progression of colorectal adenocarcinoma that originates from colorectal epithelial cells remains to be elucidated. In this study, TCRαβ and TCRγδ ‐positive T lymphocyte‐deficient mice (homozygous TCRα and TCRδ‐gene knockout mice) and the background wild‐type mice were administered azoxymethane, and the formation of macroscopic tumors and microscopic aberrant crypt foci in colorectal mucosa were compared among the three types of mice. Well‐differentiated adenocarcinoma appeared 5 months after 5 administrations of azoxymethane (10 mg/kg weight) only in a few TCRδ‐gene knockout mice and the frequency of the carcinoma‐bearing mice was increased at 7 and 9 months after the administration. Aberrant crypt foci were also detected in the colorectal mucosa of TCRδ‐gene knockout mice to a greater extent than in colorectal mucosa of TCRδ‐gene knockout mice 1 month after the azoxymethane administration. These results suggest that TCRγδ ‐positive T lymphocytes, which are present mainly in the intraepithelial space, play a role in suppression of the formation and progression of colorectal adenocarcinoma in mice.