Enhanced formation of azoxymethane-induced colorectal adenocarcinoma in gammadelta T lymphocyte-deficient mice.
T cell receptor (TCR) gammadelta-positive T lymphocytes, which are localized mostly within the intraepithelial space of intestinal epithelium, have been suggested to play a role in maintaining the normal configuration of intestinal epithelium. However, the role of TCRgammadelta-positive T lymphocytes in the formation and progression of colorectal adenocarcinoma that originates from colorectal epithelial cells remains to be elucidated. In this study, TCRalphabeta and TCRgammadelta-positive T lymphocyte-deficient mice (homozygous TCRa and TCRd-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 TCRd -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 TCRd -gene knockout mice to a greater extent than in colorectal mucosa of TCRa-gene knockout mice 1 month after the azoxymethane administration. These results suggest that TCRgammadelta-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.
Matsuda
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Institute of Clinical Research, National Kure Medical Center, Kure, Hiroshima 737-0023, Japan. matsudas@kure-nh.go.jp
Kudoh
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Katayama
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D000230:Adenocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D006720:Homozygote; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency*; D013601:T-Lymphocytes / Q000502:physiology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D001397:Azoxymethane