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 maintained germfree or colonized with a limited number of intestinal bacteria failed to develop inflammatory bowel disease (IBD)-like lesions. Evidently, inflammation in these mice does not develop spontaneously or result from a generalized antigenic stimulation, but rather requires induction by a heretofore unidentified specific stimulus. We describe the development of IBD-like lesions in germfree TCR-alpha-deficient mice monoassociated with the protozoan Cryptosporidium parvum. Lesions were seen in distal ileum, cecum, and colon and were most severe in the cecum. A prominent leukocytic infiltrate within 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 which expressed surface IgD (ie, conventional B lymphocytes). It has been proposed that antigenic stimulation by a microorganism(s) is needed to initiate intestinal inflammation in TCR-alpha-deficient mice. Our results indicate that a single microbial species, C. parvum, is capable of triggering the development of IBD-like lesions in germfree TCR-alpha-deficient mice.
Sacco
R E
RE
Veterinary Medical Research Institute, Iowa State University, Ames, USA. rsacco@nadc.ars.usda.gov
Haynes
J S
JS
Harp
J A
JA
Waters
W R
WR
Wannemuehler
M J
MJ
D000818:Animals; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000472:pathogenicity*; D005243:Feces / Q000469:parasitology; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000469:parasitology*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000502:physiology*
D016693:Receptors, Antigen, T-Cell, alpha-beta