Acetylcholine receptor-reactive T cells in myasthenia gravis: evidence for the involvement of different subpopulations of T helper cells.
Patients with myasthenia gravis have a high prevalence of acetylcholine receptor-specific T lymphocytes in the peripheral blood. Our earlier study shows that these T lymphocytes are stimulated to secrete interferon (IFN)-gamma and interleukin (IL)-2 in response to the autoantigen. Such stimulated T cells may be subdivided into different subsets according to the pattern of cytokine production. In the present study we have investigated the subpopulations of cells by analyzing their IL-4, IFN-gamma and IL-2 secretion pattern. Autoantigen-stimulated IL-4 secretion was found in 55% of the patients, IFN-gamma secretion in 86% and IL-2 secretion in 72%. T lymphocytes from all patients who responded with increased IL-2 secretion also showed increased IFN-gamma secretion. Stimulated IL-4 secretion was detected both in the presence and absence of stimulated IFN-gamma secretion. Depletion of monocytes/macrophages from peripheral blood mononuclear cell preparation and treatment of the cells with a mouse anti-human HLA-DR antibody abolished the secretion of IFN-gamma and IL-4. There were positive correlations between the numbers of IFN-gamma- and IL-2-secreting T cells and the numbers of B cells secreting antibodies against the acetylcholine receptor. Our results show that acetylcholine receptor-stimulated T lymphocytes secrete IL-4, IFN-gamma and/or IL-2. This T cell response is major histocompatibility complex (MHC) class II-restricted and monocyte/macrophage-dependent. Our study indicates that both Th1/Th2 or Th0 subpopulations of the T lymphocytes are involved in the autoimmune response in myasthenia gravis.
Yi
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Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
Ahlberg
R
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Pirskanen
R
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Lefvert
A K
AK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002038:Bungarotoxins / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*
D000906:Antibodies; D002038:Bungarotoxins; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007378:Interleukins; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins