Oligoclonal Th2-biased betabeta T cells induce murine inflammatory bowel disease.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Oligoclonal Th2-biased betabeta T cells induce murine inflammatory bowel disease.

Immunol Res. 1999;20(3):237-42. Unique Identifier : AIDSLINE MED/20203907
Takahashi I; Lijima H; Kishi D; Kiyono H; Department of Mucosal Immunology, Research Institute for; Microbial Diseases, Osaka University, Suita-Osaka, Japan.; snatum@biken.osaka-u.ac.jp

Abstract: 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.

Keywords: JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL Animal Antibodies, Monoclonal/IMMUNOLOGY/THERAPEUTIC USE Colon/METABOLISM CD4-Positive T-Lymphocytes/*IMMUNOLOGY/METABOLISM Disease Models, Animal Electrophoresis, Gel, Two-Dimensional Ileum/METABOLISM Inflammatory Bowel Diseases/DRUG THERAPY/GENETICS/*IMMUNOLOGY Interleukin-4/IMMUNOLOGY Mice Mice, Inbred C57BL Mice, Knockout Polymorphism, Single-Stranded Conformational Receptors, Antigen, T-Cell, alpha-beta/*DEFICIENCY/GENETICS Reverse Transcriptase Polymerase Chain Reaction Spleen/METABOLISM Th2 Cells/*IMMUNOLOGY/METABOLISM

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