CD4 T cells monospecific to ovalbumin produced by Escherichia coli can induce colitis upon transfer to BALB/c and SCID mice

Although some animal models suggest an involvement of CD4 T cells reactive to luminal microrbial antigen(s) for the pathogenesis of inflammatory bowel diseases (IBD), direct linkage between microflora-driven clonal expansion of CD4 T cells and the development of colitis has not been well studied. He re, BALB/c and SCID mice were given CD4 T cells purified from Rag-2(-/-) mi ce crossed to transgenic mice expressing TCR specific to ovalbumin (OVA) th en administered with antibiotic-resistant Escherichia coli producing OVA (E COVA) or LacZ (ECLacZ) via the rectum. The ECOVA-inoculated BALB/c and SCID mice developed a subacute colitis with microscopic features of distortion of crypt architecture, loss of goblet cells, and focal infiltration by mono nuclear cells in the lamina propria (LP) and submucosa. Expanding OVA-speci fic CD4 T cells were detected in colonic follicles of mice with ECOVA. Earl y in colitis, OVA-specific CD4 T cells producing IFN-gamma predominate in t he LP of the colon, which was followed by an emergence of OVA-specific CD4 T cells producing IL-4 and IL-10 at a later time point. Co-transfer of an I L-10-secreting OVA-specific CD4 T cell line prevented colitis. Thus, an exp ansion of CD4 T cells monospecific to OVA, an antigen non-cross-reactive to colonic tissue, can mediate both induction and inhibition of the colitis w hich was associated with hyperplasia of lymph follicles.