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  • Title: Clonal expansion of CD4+ TCRbetabeta+ T cells in TCR alpha-chain- deficient mice by gut-derived antigens.
    Author: Takahashi I, Iijima H, Katashima R, Itakura M, Kiyono H.
    Journal: J Immunol; 1999 Feb 01; 162(3):1843-50. PubMed ID: 9973450.
    Abstract:
    A population of CD4+ alpha-beta+ T cells increases in the mucosal and peripheral lymphoid tissues of TCRalpha-chain-deficient mice with inflammatory bowel disease. The alpha-beta+ T cells, which produce predominantly IL-4, mediate the proliferation of colonic epithelial crypts and the infiltration of large numbers of IgA-producing plasma cells into the lamina propria of the colon. To examine whether enteric Ags were recognized by a population of monoclonal alpha-beta+ T cells leading to the intestinal inflammation, we examined the usage and clonotypes of TCR expressed by the alpha-beta+ T cells in TCRalpha-chain-deficient mice with inflammatory bowel disease. Analyses of immunoprecipitates by two dimensional electrophoresis and single-cell RT-PCR revealed that TCR of the alpha-beta+ T cells was a homodimer of beta-chains that was capable of recognizing luminal bacterial Ags. PCR single-strand conformation polymorphism analysis of TCR Vbeta transcripts revealed monoclonal accumulation of the alpha-beta+ T cells in the colonic lamina propria of the diseased mice. DNA sequencing revealed the accumulation of the alpha-beta+ T cells with the same CDR3 sequences in the colon. These findings suggest that the pathogenic CD4+ alpha-beta+ T cells expressing a homodimeric form of the TCRbeta-chains can be clonally expanded upon the stimulation with gut-derived Ags.
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