An accessory role of TCRγδ+ cells in the exacerbation of inflammatory bowel disease in TCRα mutant mice

Abstract

T cell receptor α mutant (TCRα-/-) mice, which spontaneously develop colitis under conventional conditions, did not show any signs of colitis under germ-free conditions, leaving TCRα-β+ cells (βdim cells) and TCRγδ+ cells much reduced. Moreover, TCRα-/- mice with alymphoplastic mutation (alylaly TCRα-/- mice), which lack Peyer's patches and peripheral lymph nodes, did not suffer from colitis. While both βdim cells and TCRγδ+ cells were present in the colons of alylaly TCRα-/- mice and aly/+ TCRα-/- mice, cytotoxicity of colonic TCRγδ+ cells in alylaly TCRα-/- mice was almost abolished. Transfer of TCRγδ+ cells from TCRα-/- mice into scid/scid mice or alylaly TCRα-/- mice could not induce colitis, but injection of anti-TCRδ mAb into TCRα-/- mice prevented colitis from developing. Finally, TCRα-/- mice expressing transgenic (Tg) KN6-TCRγδ hardly developed colitis, accompanied by colonization of non-cytotoxic Tg TCRγδ+ cells in their colonic mucosa. These results demonstrate that intestinal resident TCRγδ+ cells may be involved in the exacerbation of inflammatory bowel disease in TCRα-/- mice.