Prevalence of an ulcerative colitis-associated CD8(+) T cell receptor beta-chain CDR3-region motif and its association with disease activity

The normal human intestinal mucosa contains clonal T cell expansions. Clona l populations of T cells can be determined through evaluation of the idioty pic, hypervariable region of their T cell receptor (TCR). We have previousl y reported that there exists a highly conserved TCR pattern among intestina l CD8(+) T cells in the majority of ulcerative colitis (UC) patients underg oing colectomy that was not present in normal control individuals. This TCR pattern, or motif, was characterized by particular beta -chain usage (TCRB V3 and TCRBJ1S6) and a defined length in the hypervariable third complement arity determining region (CDR3). The aim of this study was to assess the mo tifs relationship to disease activity. Subjects were 66 with UC, 19 with Cr ohn's disease, 14 inflammatory controls, and 6 normal controls. cDNA and gD NA were prepared from colonic biopsies and paraffin blocks, respectively, o btained from study subjects and used to assess TCRBV CDR3 region length and usage, as well as for cloning and sequencing of TCRs. The TCRBV CDR3 regio n was present in 25 of a series of 48 UC subjects but only 3 of 19 Crohn's disease patients and 3 of 14 inflammatory controls. The motif was more comm on in UC than either Crohn's disease or inflammatory controls (chi (2) = 7. 5, P = 0.006, and chi (2) = 4.1, P = 0.04, respectively). The motif's prese nce was not dependent upon histologic disease activity (either active or in active UC). Clinical UC disease activity was also not significantly associa ted with an increased presence of the motif in 14 paired biopsies, which we re taken during times of clinical activity or inactivity. There was a trend toward persistence of the motif, as it was present in 6 of 14 subjects ove r a 3- to 6-month time period. The previously described UC-associated TCRBV CDR3 region motif located in the intestinal CD8(+) T-cell subset is found in a significant proportion of UC subjects. The TCR motif does not signific antly discriminate active from inactive disease states. The persistent and diffuse nature of this TCR-associated motif in UC suggests that an ongoing T-cell response to a particular antigen(s) is occuring in this disorder.