Oligoclonal Th2-biased betabeta T cells induce murine inflammatory bowel disease.
A population of CD4+ T cells with TCR beta-chain without TCR alpha-chain (CD4+, betabeta T cells) producing Th2-type cytokines increased in the mucosal and peripheral tissues of TCR alpha-chain deficient mice with inflammatory bowel disease (IBD). Analysis of TCR-beta immunoprecipitates by two-dimensional electrophoresis and RT-PCR revealed TCR of the CD4+ T cells was a homodimer of TCR beta-chains. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses of TCR Vbeta-chain transcripts of the betabeta T cells revealed monoclonal to oligoclonal accumulation of the cells in the colon, suggesting clonal expansion of the mucosal betabeta T cells upon the stimulation with gut-derived antigens. The homodimer of TCR beta-chains on the betabeta T cells was a biologically functional receptor that transduced activation signals provided by MHC-class II-associated peptidic antigens and superantigens. Treatments of the mutant mice with mAb against TCR beta or IL-4 suppressed the onset of IBD. These findings suggest that the generation of oligoclonal Th2-type betabeta T cells plays a critical role for the development of IBD.
Takahashi
I
I
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita-Osaka, Japan. snatum@biken.osaka-u.ac.jp
Lijima
H
H
Kishi
D
D
Kiyono
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D007082:Ileum / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4