CHARACTERIZATION OF THE SYNOVIAL T-CELL RESPONSE TO VARIOUS RECOMBINANT YERSINIA ANTIGENS IN YERSINIA ENTEROCOLITICA-TRIGGERED REACTIVE ARTHRITIS - HEAT-SHOCK-PROTEIN-60 DRIVES A MAJOR IMMUNE-RESPONSE

Objective. In Yersinia enterocolitica-triggered reactive arthritis (Ye rsinia ReA), the synovial T cell response is primarily directed agains t bacterial components, which are mostly unknown. This study was perfo rmed to investigate the synovial proliferative T cell response to a pa nel of recombinant Yersinia antigens in patients with I Yersinia ReA a nd in controls. Methods. Synovial fluid mononuclear cells (SFMC) were obtained from 4 patients with Yersinia ReA and from 14 patients with a rthritides of different etiology, SFMC were stimulated with 5 recombin ant Yersinia antigens (the 19-kd urease beta subunit, 13-kd ribosomal L23 protein, 32-kd ribosomal L2 protein, 18-kd outer membrane protein H, and Y enterocolitica heat-shock protein 60 [hsp60]), and with human , Chlamydia trachomatis, and Borrelia burdorferi hsp60. Three T cell c lones specific for Y enterocolitica hsp60 were generated from 1 patien t with Yersinia ReA. Antigen-induced cytokine release was measured by enzyme-linked immunosorbent assay. Results. SFMC from all 4 patients w ith Yersinia ReA responded to each of the Yersinia antigens except the 13-kd protein. These antigens were also recognized by SFMC from a sub group of patients with undifferentiated arthritis (n = 4), but not bg SFMC from other patients with arthritis of different etiology (n = 10) . Y enterocolitica hsp60 induced the strongest proliferative response in all cases. Two types of hsp60-reactive T cell clones could be obtai ned. One clone responded to all hsp60 variants, including the human va riant, and showed a type 2 T helper (Th2)-like cytokine-secretion patt ern. In contrast, another clone with specificity for the bacterial hsp 60 proteins, but not the human equivalent, reacted, with a more Th1-li ke pattern. Conclusion. In Y enterocolitica-triggered ReA, at least 4 immunodominant T cell antigens exist, which might be used in lymphocyt e proliferation assays to identify patients with Yersinia ReA. The hsp 60 is a strong antigen, inducing both bacteria-specific and potentiall y autoreactive CD4+ T cells of both the Th1 and Th2 type.