An accessory role of TCR gamma delta(+) cells in the exacerbation of inflammatory bowel disease in TCR alpha mutant mice

T cell receptor alpha mutant (TCR alpha (-/-)) mice, which spontaneously de velop colitis under conventional conditions, did not show any signs of coli tis under germ-free conditions, leaving TCR alpha (-)beta (+) cells (beta ( dim) cells) and TCR gamma delta (+) cells much reduced. Moreover, TCR alpha (-/-) mice with alymphoplastic mutation (aly/aly TCR alpha (-/-) mice), wh ich lack Peyer's patches and peripheral lymph nodes, did not suffer from co litis. While both beta (dim) cells and TCR gamma delta (+) cells were prese nt in the colons of aly/aly TCR alpha (-/-) mice and aly/+ TCR alpha (-/-) mice, cytotoxicity of colonic TCR gamma delta (+) cells in aly/aly TCR alph a (-/-) mice was almost abolished. Transfer of TCR gamma delta (+) cells fr om TCR alpha (-/-) mice into scid/scid mice or aly/aly TCR alpha (-/-) mice could not induce colitis, but injection of anti-TCR delta mAb into TCR alp ha (-/-) mice prevented colitis from developing. Finally, TCR alpha (-/-) m ice expressing transgenic (Tg) KN6-TCR gamma delta hardly developed colitis , accompanied by colonization of non-cytotoxic Tg TCR gamma delta (+) cells in their colonic mucosa. These results demonstrate that intestinal residen t TCR gamma delta (+) cells may be involved in the exacerbation of inflamma tory bowel disease in TCR alpha (-/-) mice.