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 (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.
Mertz
A K
AK
Free University, Berlin, Germany.
Ugrinovic
S
S
Lauster
R
R
Wu
P
P
Grolms
M
M
Böttcher
U
U
Appel
H
H
Yin
Z
Z
Schiltz
E
E
Batsford
S
S
Schauer-Petrowski
C
C
Braun
J
J
Distler
A
A
Sieper
J
J
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*
D000942:Antigens, Bacterial; D018834:Chaperonin 60; D016207:Cytokines; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011994:Recombinant Proteins