Abnormal T cell responses to bacterial superantigens in Behçet's disease (BD).
This study examines the nature of T cell hypersensitivity in BD. Highly purified T cells from 32 BD patients, from 29 rheumatoid arthritis (RA) patients and from 14 healthy individuals were cultured with various concentrations of Staphylococcal enterotoxins (SE) B and C1 in the presence of monocytes for 5 days, after which the production of interferon-gamma (IFN-gamma) was assessed. High concentrations of SE (1 ng/ml) stimulated BD T cells as well as control T cells to produce comparably high amounts of IFN-gamma, whereas low concentrations of SE (1 pg/ml) stimulated BD T cells much more effectively than normal or RA T cells. The hypersensitivity of BD T cells to low concentrations of SEC1 was restored with RA monocytes instead of BD monocytes, whereas BD monocytes could not elicit the SEC1-induced IFN-gamma production of RA T cells. Moreover, there were no significant differences between BD T cells and RA T cells in monocyte-independent IFN-gamma production stimulated with low or high concentrations of immobilized anti-CD3, or in the monocyte-mediated enhancement of IFN-gamma production stimulated with a low concentration of immobilized anti-CD3. These results confirm that T cell hypersensitivity is not confined to certain specific antigens in BD. More importantly, the data strongly suggest that abnormalities in signal transduction triggered by perturbation of T cell receptors, but not in that induced by cross-linking of CD3 molecules nor in that delivered through costimulation molecules, play an important role in the pathogenesis of BD.
Hirohata
S
S
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Hashimoto
T
T
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001528:Behcet Syndrome / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013210:Staphylococcus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004768:Enterotoxins; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D007371:Interferon-gamma