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.