title: 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.
abstract: OBJECTIVE
  In Yersinia enterocolitica-triggered reactive arthritis (Yersinia ReA), the synovial T cell response is primarily directed against bacterial components, which are mostly unknown. This study was performed to investigate the synovial proliferative T cell response to a panel of recombinant Yersinia antigens in patients with Yersinia ReA and in controls.
  
  
  METHODS
  Synovial fluid mononuclear cells (SFMC) were obtained from 4 patients with Yersinia ReA and from 14 patients with arthritides of different etiology. SFMC were stimulated with 5 recombinant 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 burgdorferi hsp60. Three T cell clones specific for Y. enterocolitica hsp60 were generated from 1 patient with Yersinia ReA. Antigen-induced cytokine release was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  SFMC from all 4 patients with Yersinia ReA responded to each of the Yersinia antigens except the 13-kd protein. These antigens were also recognized by SFMC from a subgroup of patients with undifferentiated arthritis (n = 4), but not by 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 obtained. One clone responded to all hsp60 variants, including the human variant, and showed a type 2 T helper (Th2)-like cytokine-secretion pattern. In contrast, another clone with specificity for the bacterial hsp60 proteins, but not the human equivalent, reacted with a more Th1-like pattern.
  
  
  CONCLUSIONS
  In Y. enterocolitica-triggered ReA, at least 4 immunodominant T cell antigens exist, which might be used in lymphocyte proliferation assays to identify patients with Yersinia ReA. The hsp60 is a strong antigen, inducing both bacteria-specific and potentially autoreactive CD4+ T cells of both the Th1 and Th2 type.
authors.affiliation: Free University, Berlin, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Mertz
authors.forename: S
authors.initials: S
authors.lastname: Ugrinovic
authors.forename: R
authors.initials: R
authors.lastname: Lauster
authors.forename: P
authors.initials: P
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Grolms
authors.forename: U
authors.initials: U
authors.lastname: Böttcher
authors.forename: H
authors.initials: H
authors.lastname: Appel
authors.forename: Z
authors.initials: Z
authors.lastname: Yin
authors.forename: E
authors.initials: E
authors.lastname: Schiltz
authors.forename: S
authors.initials: S
authors.lastname: Batsford
authors.forename: C
authors.initials: C
authors.lastname: Schauer-Petrowski
authors.forename: J
authors.initials: J
authors.lastname: Braun
authors.forename: A
authors.initials: A
authors.lastname: Distler
authors.forename: J
authors.initials: J
authors.lastname: Sieper
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000502:physiology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D016918:Arthritis, Reactive / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D018834:Chaperonin 60 / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D000091402:Prohibitins; D011994:Recombinant Proteins; D012016:Reference Values; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D018834:Chaperonin 60; D016207:Cytokines; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011994:Recombinant Proteins