Cryptosporidium parvum initiates inflammatory bowel disease in germfree T cell receptor-alpha-deficient mice

Flora-bearing mice with targeted disruption of T cell receptor (TCR)-alpha or -beta genes spontaneously develop intestinal inflammation with features similar to ulcerative colitis in humans. TCR-alpha-deficient mice maintaine d germfree or colonized with a limited number of intestinal bacteria failed to develop inflammatory bowel disease (IBD)-like lesions. Evidently, infla mmation in these mice does not develop spontaneously or result from a gener alized antigenic stimulation, but rather requires induction by a heretofore unidentified specific stimulus. We describe the development of IBD-like le sions in germfree TCR-alpha-deficient mice monoassociated with the protozoa n Cryptosporidium parvum. Lesions were seen in distal ileum, cecum, and col on and were most severe in the cecum, A prominent leukocytic infiltrate wit hin the lamina propria was a common characteristic of the lesions observed in the C, parvum-infected germfree TCR-alpha-deficient mice, The leukocytic infiltrate was composed of aggregates of B220(+) cells, the majority of wh ich expressed surface IgD (ie, conventional B lymphocytes), It has been pro posed that antigenic stimulation by a microorganism(s) is needed to initiat e intestinal inflammation in TCR-alpha-deficient mice. Our results indicate that a single microbial species, C. parvum, is capable of triggering the d evelopment of IBD-like lesions in germfree TCR-alpha-deficient mice.