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 (-/...

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Bibliographic Details
Published in:European journal of immunology 2001-04, Vol.31 (4), p.980-988
Main Authors: Kawaguchi-Miyashita, M, Shimada, S, Kurosu, H, Kato-Nagaoka, N, Matsuoka, Y, Ohwaki, M, Ishikawa, H, Nanno, M
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Cells, Cultured
Colon - immunology
Colon - pathology
Crosses, Genetic
Cytotoxicity, Immunologic
Female
Fluorescent Antibody Technique
Gene Deletion
Germ-Free Life
Inflammation - genetics
Inflammation - immunology
Inflammation - pathology
Inflammatory Bowel Diseases - genetics
Inflammatory Bowel Diseases - immunology
Inflammatory Bowel Diseases - pathology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Mutant Strains
Mice, SCID
Organ Size
Receptors, Antigen, T-Cell, alpha-beta - deficiency
Receptors, Antigen, T-Cell, alpha-beta - genetics
Receptors, Antigen, T-Cell, gamma-delta - genetics
Receptors, Antigen, T-Cell, gamma-delta - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
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Summary: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.
ISSN:0014-2980