SELECTIVE EXPANSION OF SPECIFIC T-CELL RECEPTORS IN THE INFLAMED COLON OF CROHNS-DISEASE

To identify disease-specific T cell changes that occur in Crohn's dise ase (CD), the T cell receptor BV repertoires of lamina propria lymphoc ytes (LPL) isolated from both the inflamed and ''disease-inactive'' co lons of seven CD patients were compared by the quantitative PCR and DN A sequence analysis, It was observed that the BV repertoires of LPL is olated from the disease-active and disease-inactive parts of the colon from the same individual were very different. Furthermore, nearly all of the differences occurred in CD4(+) LPL, with very few differences in the CD8(+) population of LPL. Although the pattern of BV segments t hat was increased in disease-active tissue relative to disease-inactiv e tissue was different for all seven CD patients, there were several B V segments that increased uniformly in the disease-active tissue of al l seven individuals, CDR3 length analysis and DNA sequencing of these BV segments revealed that in six of the seven CD patients there was a striking degree of oligoclonality that was absent from disease-inactiv e tissue of the same individual. These observations suggest that at le ast some of the inflammation in CD is the result of responses by CD4() T cells to specific antigens. The isolation of such inflammation-spe cific CD4(+) T cells may make it possible to identify the antigens tha t are responsible for the inflammatory process in CD and provide a bet ter understanding of its pathogenesis.