Presynaptic membrane receptor-reactive T lymphocytes in myasthenia gravis.
The majority of patients with myasthenia gravis were shown to have T and B cells specific for a beta-bungarotoxin binding protein, presynaptic membrane receptor (PsmR). Such autoreactive T cells may be subdivided into different subsets according to the pattern of cytokine production. In this study the authors examined the subpopulation of the T cells by analysing their IFN-gamma and/or IL-4 secretion pattern. T cell response to human muscle acetylcholine receptor (AChR) was examined in parallel. PsmR-stimulated IFN-gamma secretion was found in 60%, and IL-4 secretion in 48% of the patients. Cells stimulated to secrete both IFN-gamma and IL-4 or IFN-gamma only were the most common patterns. Treatment of the cells with a mouse anti-human HLA-DR antibody abolished the secretion of cytokines. There was a positive correlation between the numbers of PsmR-reactive and AChR-reactive T cells. In conclusion, the results show that PsmR-stimulated T cells secreted IFN-gamma and/or IL-4. This T cell response is MHC class II restricted. Thus, this study indicates that both Th1/Th2 or Th0 subsets of the T cells are involved in the autoimmune response in the disease.
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Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
Pirskanen
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Lefvert
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AK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002038:Bungarotoxins / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000276:immunology; D011950:Receptors, Cholinergic / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism*; D013570:Synaptic Membranes / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; D006684:HLA-DR Antigens; D011950:Receptors, Cholinergic; D017661:Receptors, Presynaptic; D015847:Interleukin-4; D007371:Interferon-gamma