T cells with specificity for idiotypic determinants on human monoclonal autoantibodies in myasthenia gravis.
The activation of T cells from 46 patients with myasthenia gravis and 28 healthy individuals by two human monoclonal autoantibodies was studied. B-cell clones were produced by transformation of peripheral lymphocytes from a patient using Epstein-Barr virus and subsequent cloning. Two myasthenia-specific autoantibodies, one anti-receptor-antibody and one antiidiotypic antibody, both carrying separate recurrent idiotopes, were used in this study. Single activated T cells were identified by their secretion of IL2 and IFN gamma using a cell enzyme-linked-immunosorbent technique. The idiotypic antibody activated T cells in patients but not in most of the controls at concentrations of 1 pg/ml and 10 pg/ml. High concentrations of antibody resulted in T-cell activation in both groups. A similar dose-response pattern was recorded using the antiidiotypic antibody. Incubation with the idiotypic antibody resulted in T-cell stimulation, measured as numbers of IFN gamma-secreting cells that exceeded the mean +2 SD of controls, in 78% of patients and in 7% of the healthy individuals (p less than 0.001). The antiidiotypic antibody activated T cells in 50% of patients and in 4% of the healthy individuals (p less than 0.001). T-cell activation measured as numbers of IL2-secreting cells showed a difference between patients and controls which was as significant as for IFN gamma secretion. The results demonstrate the presence of T cells with specificity for disease-specific determinants on idiotypic and antiidiotypic antibodies in myasthenia gravis.
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Immunological Research Laboratory, Karolinska Hospital, Stockholm.
Ahlberg
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Lefvert
A K
AK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2; D007371:Interferon-gamma