Molecular biology of oligoclonal ββィイD1+ィエD1 T cells in murine inflammatory bowel disease

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A population of CD4ィイD1+ィエD1 T cells with TCR β-chain without TCR α-chain (CD4ィイD1+ィエD1,ββィイD1+ィエD1 T cells) producing Th2-type cytokines increased in the mucosal and peripheral tissues of TCR α-chain deficient mice with inflammatory bowel disease (IBD). Analysis of TCR-β immunoprecipitates by two-dimensional electrophoresis and RT-PCR revealed TCR of the CD4ィイD1+ィエD1 T cells was a homodimer of TCR β-chains. PCR-SSCP analyses of TCR νβ-chain transcripts of the ββィイD1+ィエD1 T cells revealed monoclonal to oligoclonal accumulation of the cells in the colon, suggestingclonal expansion of the mucosal ββィイD1+ィエD1 T cells upon the stimulation with gut-derived antigens. The homodimer of TCR β-chains on the ββィイD1+ィエD1 T cells was a biologically functional receptor which transducedactivation signals provided by MHC-class ll-associated peptidic antigens and superantigens. The importance of the Th2-biased ββィイD1+ィエD1 T cells was also supported by the finding that treatments of the mutant mice with mAb against TCR βor lL-4 suppressed the onset of IBD. The Th2-biased cytokine production by the ββィイD1+ィエD1 T cells in IBD mice could be attributed to the high incidence of Bacteroides vulgatus. Rectal administration of non-diseased mice with B. vulgatus resulted in the development of Th2-type ββィイD1+ィエD1 T cell-induced colitis. These findings suggest that the generation of oligoclonal Th2-type ββィイD1+ィエD1 T cells plays a critical role for the development of IBD.