Oligoclonal Th2-biased beta beta T cells induce murine inflammatory bowel disease

A population of CD4(+) T cells with TCR beta-chain without TCR alpha-chain (CD4(+), beta beta T cells) producing Th2-type cytokines increased in the m ucosal and peripheral tissues of TCR alpha-chain deficient mice with inflam matory bowel disease (IBD). Analysis of TCR-beta immunoprecipitates by two- dimensional electrophoresis and RT-PCR revealed TCR of the CD4(+) T cells w as a homodimer of TCR beta-chains. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses of TCR V beta-chain transcrip ts of the beta beta T cells revealed monoclonal to oligoclonal accumulation of the cells in the colon, suggesting clonal expansion of the mucosal beta beta T cells upon the stimulation with gut-derived antigens. The homodimer of TCR beta-chains on the beta beta T cells was a biologically functional receptor that transduced activation signals provided by MHC-class II-associ ated peptidic antigens and superantigens. Treatments of the mutant mice wit h mAb against TCR beta or IL-4 suppressed the onset of IBD. These findings suggest that the generation of oligoclonal Th2-type beta beta T cells plays a critical role for the development of IBD.