title: T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment.
abstract: 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.
authors.affiliation: Imperial Cancer Research Fund, London, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Dianda
authors.forename: A M
authors.initials: AM
authors.lastname: Hanby
authors.forename: N A
authors.initials: NA
authors.lastname: Wright
authors.forename: A
authors.initials: A
authors.lastname: Sebesteny
authors.forename: A C
authors.initials: AC
authors.lastname: Hayday
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D004198:Disease Susceptibility; D005856:Germ-Free Life / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta