T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment

Am J Pathol. 1997 Jan;150(1):91-7.


Mice with null mutations in cytokine or T cell receptor (TCR) genes develop intestinal inflammation. In the case of interleukin-2-/- and interleukin-10-/- mice it has been demonstrated that normal intestinal bacterial flora can cause gut pathology. TCR-alpha-/- mice not only develop colitis but also produce a strong antibody response to self-antigens, such as double-stranded DNA. It is therefore important to establish whether the intestinal inflammation develops spontaneously or is induced by luminal antigens. To address this issue, a germ-free colony of TCR-alpha-/- mice was derived and compared with TCR-alpha-/- mice kept in conventional specific-pathogen-free conditions. Although specific-pathogen-free animals developed colitis with a high level of penetrance, there was no evidence of intestinal pathology in germ-free animals. Furthermore, intestinal inflammation was not seen in TCR-alpha-/- mice colonized with a limited bacterial flora consisting of Lactobacillus plantarum, Streptococcus faecalis, S. faecium, and/or Escherichia coli. We conclude that intestinal inflammation in TCR-alpha-/- mice does not occur spontaneously nor does it result from the presence of bacteria, per se, but rather it is initiated by a specific organism or group of organisms normally present in the gut flora that have yet to be identified.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Colitis / genetics*
  • Colitis / microbiology
  • Colitis / pathology*
  • Disease Susceptibility
  • Germ-Free Life / genetics*
  • Germ-Free Life / immunology*
  • Mice
  • Mice, Mutant Strains / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Specific Pathogen-Free Organisms


  • Receptors, Antigen, T-Cell, alpha-beta