Increased expression of TCR Vβ5.1 and 8 in mucosal T‐cell Lines cultured from patients with Crohn disease

Abstract

Background: Characterization of the T‐cell receptor variable β chain (Vβ) repertoire in inflamed mucosa has been used to identify disease‐relevant T‐cell populations and antigens in Crohn disease (CD). In vitro expansion of mucosal T cells may reveal changes in Vβ repertoire not apparent in fresh isolates and we aimed to identify Vβ subpopulations implicated in Crohn disease. Methods: In vivo activated mucosal T cells were cultivated using IL‐2 and IL‐4 from biopsies of whole colonic mucosa without use of Vβ‐modifying exogenous antigen or feeder cells. The Vβ gene expression in mucosal T‐cell cultures was determined in 30 patients with CD and 12 healthy controls using reverse transcriptase polymerase reaction (RT‐PCR) covering all 23 functional Vβ families and the Vβ receptor prevalence was evaluated by flow cytometry in selected cultures. Results: Early T‐cell cultures from both CD patients and healthy controls showed a polyclonal Vβ gene expression that narrowed during culture, which in CD cultures led to a significant over‐expression of the Vβ5.1 (P = 0.04) and Vβ8 gene segments (P = 0.03). Together with Vβ6 and Vβ18, these Vβ chains form a pattern of staphylococcal enterotoxin type E (SEE) responsive Vβ chains, also over‐expressed in CD cultures (P = 0.02). Further in vitro stimulation of CD cultures with SEE caused expansion of Vβ8 receptor positive cells together with a proinflammatory cytokine response. Conclusions: CD may be associated with (super)antigen‐specific Vβ subpopulations selected during long‐term cultivation of mucosal biopsies from inflamed colon.

• Crohn disease
• superantigens
• T‐cell culture
• TCR Vβ