Superantigen-mediated proliferation and cytotoxicity of T cells isolated from the inflammatory tissues and peripheral blood of arthritis patients.
Superantigens are thought to play a role in acute infections and in the pathogenesis of autoimmune diseases that are believed to have an infectious etiology. The effect of the superantigens staphylococcal enterotoxin A, staphylococcal enterotoxin B, and streptococcal M type 5 protein on T cells derived from inflammatory tissues and peripheral blood (PB) of arthritis patients was studied in seven rheumatoid arthritis (RA), two psoriatic arthritis, two reactive arthritis, and one ankylosing spondylitis patient. Superantigen-reactive T cells and T cell lines derived from the PB, synovial fluid (SF), and synovial membrane (SM) of all 12 arthritis tissues recognized the superantigens in an MHC-unrestricted manner. Heterogeneities in proliferation and superantigen-directed T cell cytotoxicity were observed in E+ T cells and the T cell lines. Four SF-CD4+ mycobacteria heat-shock protein 65-kDa specific T cell clones generated from an RA patient could recognize and lyse each other when pulsed with staphylococcal enterotoxin A and used as targets. From another RA patient, four SF-CD4+ T cell clones that specifically recognize autoantigens were generated with human IgG fragments or collagen type II fragments. Heterogeneities of such superantigen-mediated specific lysis were also demonstrated. The data presented by us suggest a model in which superantigens do not have to be involved in triggering the initial disease because autoreactive T cells elicited by antigen can, in the presence of superantigen, lyse cells that express MHC class II molecules, including activated T cells.
Li
S
S
Oslo Sanitetsforenings Rheumatism Hospital, Norway.
Quayle
A J
AJ
Thoen
J E
JE
Førre
O T
OT
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D015551:Autoimmunity; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D009161:Mycobacterium / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006681:HLA-D Antigens; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D018089:Superantigens; D003094:Collagen