Systemic activation and antigen-driven oligoclonal expansion of T cells ina mouse model of colitis

Transfer of CD4(+)CD45RB(high) T cells into immunodeficient mice results in both the expansion of the transferred T cells and colitis. Here we show th at colitis pathogenesis requires expression of MHC class II molecules by th e immune-deficient host, Analysis of the TCR beta repertoire of the cells f ound in the large intestine of diseased mice revealed a population with res tricted TCR diversity. Furthermore, nucleotide sequence analysis demonstrat ed the selection for particular CDR3 beta amino acid sequence motifs, Colle ctively, these data indicate that the expansion of T cells in the intestine and colitis pathogenesis are likely to require the activation of Ag-specif ic T cells, as opposed to nonspecific or superantigen-mediated events. Ther e is relatively little overlap, however, when the TCR repertoires of differ ent individuals are compared, suggesting that a number of Ags can contribut e to T cell expansion and the generation of a T cell population in the inte stine. Surprisingly, many of the expanded clones found in the large intesti ne also were found in the spleen and elsewhere, although inflammation is lo calized to the colon. Additionally, donor-derived T cells appear to be acti vated in both the intestine and the spleen at early time points after cell transfer. Together, these results strongly suggest that disease induction i n this model involves either the early and systemic activation of antigen-s pecific T cells or the rapid dispersal of T cells activated at a particular site.