An accessory role of TCRgammadelta (+) cells in the exacerbation of inflammatory bowel disease in TCRalpha mutant mice

Eur J Immunol. 2001 Apr;31(4):980-8. doi: 10.1002/1521-4141(200104)31:4<980::aid-immu980>3.0.co;2-u.

Abstract

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.

MeSH terms

  • 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

Substances

  • Antibodies, Monoclonal
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta