Synovial fluid-derived Yersinia-reactive T cells responding to human 65-kDa heat-shock protein and heat-stressed antigen-presenting cells.
Humoral and cellular immune reactions to heat-shock proteins have been implicated in the pathogenesis of arthritis. Heat-shock proteins occur in bacteria as well as all eukaryotes and have been highly conserved during evolution. Cross-reactivity between bacterial and human heat-shock proteins induced at the site of inflammation may underlie the pathogenesis of some forms of arthritis. In order to test this hypothesis, we raised and cloned a Yersinia-specific T cell line from the synovial fluid lymphocytes of a patient with Yersinia-induced reactive arthritis. From this line we obtained a CD4+ T cell clone that proliferated in response to Yersinia antigens and both to the mycobacterial and the human 65-kDa heat-shock protein. This T cell clone also proliferated in response to autologous heat-stressed antigen-presenting cells as well as to synovial fluid mononuclear cells from the inflamed joint, thus showing true autoreactivity against endogenously synthetized self-antigen. These results demonstrate the induction of an autoimmune T cell response by a natural bacterial infection and support the important role of heat-shock proteins in the pathogenesis of immune-mediated arthritis.
Hermann
E
E
I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität, Mainz, FRG.
Lohse
A W
AW
Van der Zee
R
R
Van Eden
W
W
Mayet
W J
WJ
Probst
P
P
Poralla
T
T
Meyer zum Büschenfelde
K H
KH
Fleischer
B
B
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D016918:Arthritis, Reactive / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D012486:Salmonella typhimurium / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology*; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology; D015007:Yersinia / Q000276:immunology; D001616:beta-Galactosidase / Q000276:immunology
D006360:Heat-Shock Proteins; D013744:Tetanus Toxin; D001616:beta-Galactosidase