The gammadeltaT cells have been known to play an important role in the regulation of the mucosal immune system, but the relationship between these cells and the pathogenesis of Crohn's disease (CD) has remained obscure. We now demonstrate the T-cell receptor (TCR) Vdelta2 gene transcripts characterize antigenic immune response in the intestinal mucosa from patients with CD. TCR Vdelta2 gene transcripts of six patients with CD and six controls were subcloned and 20 randomly selected clones from each sample were subjected to nucleotide sequencing. Sequence analysis demonstrated that the different clones in the intestinal mucosa of CD were significantly increased (11.833 +/- 0.946) compared to controls (7.167 +/- 1.470) (P = 0.0374). The presence of intraindividual dominance and oligoclonality of TCR Vdelta2 gene transcripts in normal controls appears reflect positive selection and expansion of specific gammadelta T cells in normal controls. By contrast TCR Vdelta2 gene transcripts in the intestinal mucosa of CD can express different clonotypes. We conclude that accumulation of multiple Vdelta2+ gammadelta T-cell clonotypes are involved in the pathogenesis of CD.