γδ T cells have been reported to secrete a cytokine which supports the elimination of impaired epithelial cells and to maintain the normal configuration of the intestinal epithelium. 5,6) However, the precise functions of γδ T cells have not been elucidated. Some recent studies have described the effect of γδ T cells on intestinal tumor cells. γδ T cells regulated the cytotoxic activities of NK cells and CTL, of which the targets were intestinal tumor cells.7) The frequency of tumorinfiltrated γδ T cells was lowered in human well-to-moderately differentiated colorectal adenocarcinoma, 8) suggesting a relationship between γδ T cells and the formation and progression of colorectal adenocarcinoma. Notably, γδ T cells in which the variable region on the TCRδ chain is Vδ1 (Vδ1-γδ T cells) were reported to be predominant in iIEL, to recognize the major histocompatibility complex class I-related molecules A and B (MICA and MICB) and to have cytotoxic activity against intestinal tumor cells.
9)The above report also suggests that γδ T cells in iIEL may affect the formation and progression of colorectal adenocarcinoma.The present study was designed to examine the effect of γδ T cells on the formation and progression of chemically induced colorectal adenocarcinoma using γδ T cell-deficient mice. Azoxymethane (AOM) was administered to wild-type C57BL/6 mice, αβ T cell-deficient mice (TCRα-gene knockout mice) and γδ T cell-deficient mice (TCRδ-gene knockout mice) and the formation of macroscopic tumors and microscopic aberrant crypt foci in colorectal mucosa was examined. The effect of γδ T cells on the formation and progression of colorectal adenocarcinoma is discussed in the light of the results of the present study.
MATERIALS AND METHODSMice Homozygous TCRα-gene knockout mice, 10) homozygous TCRδ-gene knockout mice 11) and wild-type C57BL/6 (the background of the knockout mice) were purchased from Jackson Laboratories (Bar Harbor, ME). The mice were bred and maintained in a clean air system (EBAC-S, Clea Japan Inc., Tokyo). Two-to 3-month-old mice (body weight: 15-20 g) were used for experiments. Induction of colorectal tumors and aberrant crypt foci For the induction of colorectal tumors, mice were administered AOM (10 mg/kg weight) intraperitoneally (i.p.) once