Synovial fibroblasts as target cells for staphylococcal enterotoxin-induced T-cell cytotoxicity.
Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology. Recently, superantigens have been implied in the pathogenesis of RA. Superantigens activate a large fraction of T cells leading to the production of cytokines and proliferation. In addition, superantigens direct cellular cytotoxicity towards major histocompatibility complex (MHC) class II-expressing cells. There is now increasing evidence that cytotoxic T cells may be involved in the pathogenesis of RA. In the inflamed synovia class II-positive synovial fibroblasts (SFC) are found. In the present study it was tested whether MHC class II-positive SFC serve as target cells for superantigen-induced cellular cytotoxicity. SFC were stimulated with interferon-gamma to express class II antigens, then they were cultivated in the presence of CD4-positive T cells with or without staphylococcal enterotoxins (SE). Cytotoxicity of T cells was measured as release of lactate dehydrogenase from SFC. Specific cytotoxicity was only found in the presence of class II-positive SFC depending on the dose of SE. Maximum lysis was seen after 20 hr. T-cell cytotoxicity was inhibited by antibodies to MHC class II antigens. The data suggest that class II-positive SFC not only function as accessory cells for SE-mediated T-cell proliferation and interleukin-2 production but may also be the targets of superantigen-mediated cellular cytotoxicity.
Kraft
M
M
Institute of Immunology, University of Heidelberg, Germany.
Filsinger
S
S
Krämer
K L
KL
Kabelitz
D
D
Hänsch
G M
GM
Schoels
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018929:Cell Culture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D018089:Superantigens / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D018089:Superantigens; C049463:enterotoxin E, Staphylococcal