L. Dianda et al., T-CELL RECEPTOR-ALPHA-BETA-DEFICIENT MICE FAIL TO DEVELOP COLITIS IN THE ABSENCE OF A MICROBIAL ENVIRONMENT, The American journal of pathology, 150(1), 1997, pp. 91-97
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.