Abstract
A population of CD4+ T cells with TCR β-chain without TCRα (CD4+, α-β+ T cells) increased in the mucosal and peripheral lymphoid tissues of TCRα-/- mice with inflammatory bowel disease (IBD) . Depletion of the CD4+, α-β+ T cells by the treatment of TCRα-/- mice with mAb against TCRβ suppressed the onset of IBD.
We further assessed the clonotypes of the infiltrated CD4+, α-β+ T cells in TCRα-/- mice with IBD by using a polymerase chain reaction singlestrand conformation polymorphism (PCR-SSCP) analysis of CDR3 segment of TCRβ chain. SSCP analyses of PCR-amplified TCR Vβ chain transcripts indicated that TCR Vβ repertoire of CD4+, α-β+ T cell populations in the diseased mice was relatively monoclonal to oligoclonal, and that the repertoire in the diseased colon exhibited nearly identical mobility among the individual IBD mice. However, the TCR Vβ repertoire in peripheral lymphoid tissues such as spleen and mesenteric lymph nodes (MLN) was more divergent compared to that of the colon, suggesting that the mucosal CD4+, α-β+ T cells can be clonally expanded upon the stimulation with gutderived antigens. Thus, an oligoclonal population of the aberrant CD4+, α-β+ T cells is positively selected and prominently expanded in the intestinal inflammatory lesion.
