An accessory role of TCRgammadelta (+) cells in the exacerbation of inflammatory bowel disease in TCRalpha mutant mice.
T cell receptor alpha mutant (TCRalpha (-/-)) mice, which spontaneously develop colitis under conventional conditions, did not show any signs of colitis under germ-free conditions, leaving TCRalpha (-)beta (+) cells (beta (dim) cells) and TCRgamma delta (+) cells much reduced. Moreover, TCRalpha (-/-) mice with alymphoplastic mutation (aly/aly TCRalpha (-/-) mice), which lack Peyer's patches and peripheral lymph nodes, did not suffer from colitis. While both beta (dim) cells and TCRgamma delta (+) cells were present in the colons of aly/aly TCRalpha (-/-) mice and aly/+ TCRalpha (-/-) mice, cytotoxicity of colonic TCRgamma delta (+) cells in aly/aly TCRalpha (-/-) mice was almost abolished. Transfer of TCRgamma delta (+) cells from TCRalpha (-/-) mice into scid/scid mice or aly/aly TCRalpha (-/-) mice could not induce colitis, but injection of anti-TCRdelta mAb into TCRalpha (-/-) mice prevented colitis from developing. Finally, TCRalpha (-/-) mice expressing transgenic (Tg) KN6-TCRgamma delta hardly developed colitis, accompanied by colonization of non-cytotoxic Tg TCRgamma delta (+) cells in their colonic mucosa. These results demonstrate that intestinal resident TCRgamma delta (+) cells may be involved in the exacerbation of inflammatory bowel disease in TCRalpha (-/-) mice.
Kawaguchi-Miyashita
M
M
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Shimada
S
S
Kurosu
H
H
Kato-Nagaoka
N
N
Matsuoka
Y
Y
Ohwaki
M
M
Ishikawa
H
H
Nanno
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003106:Colon / Q000276:immunology / Q000473:pathology; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D005260:Female; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005856:Germ-Free Life; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D009929:Organ Size; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta