T-CELL RECEPTOR-ALPHA-BETA-DEFICIENT MICE FAIL TO DEVELOP COLITIS IN THE ABSENCE OF A MICROBIAL ENVIRONMENT

Mice with null mutations in cytokine or T cell receptor (TCR) genes de velop intestinal inflammation. In the case of interleukin-2(-/-) and i nterleukin-10(-/-) mice it has been demonstrated that normal intestina l bacterial flora can cause gut pathology. TCR-alpha(-/-) mice not onl y develop colitis but also produce a strong antibody response to self- antigens, such as double-stranded DNA. It is therefore important to es tablish whether the intestinal inflammation develops spontaneously or is induced by luminal antigens. To address this issue, a germ-free col ony of TCR-alpha(-/-) mice was derived and compared with TCR-alpha(-/- ) mice kept in conventional specific-pathogen-free conditions. Althoug h specific-pathogen-free animals developed colitis with a high level o f penetrance, there was no evidence of intestinal pathology in germ-fr ee animals. Furthermore, intestinal inflammation was not seen in TCR-a lpha(-/-) mice colonized With a limited bacterial flora consisting of Lactobacillus plantarum, Streptococcus faecalis, S. faecium, and/or Es cherichia coli We conclude that intestinal inflammation in TCR-alpha(- /-) mice does not occur spontaneously nor does it result from the pres ence of bacteria, per se, but rather it is initiated by a specific org anism or group of organisms normally present in the gut flora that har e yet to be identified.