Idiotype- and anti-idiotype-reactive T lymphocytes in myasthenia gravis. Evidence for the involvement of different subpopulations of T helper lymphocytes.
Patients with myasthenia gravis have peripheral blood T cells that are stimulated to secrete IFN-gamma and IL-2 by human monoclonal anti-acetylcholine receptor and anti-idiotypic Abs. The human CD4+ Th cells may be subdivided into different subsets according to the pattern of cytokine production. To elucidate the subgroup of T cells involved in myasthenia gravis, we have analyzed IL-4-, IFN-gamma-, and IL-2-secretion patterns induced by two human disease-specific mAbs, one idiotypic and one anti-idiotypic Ab. T cells stimulated to secrete one or more of the cytokines were found in 33 of 34 patients. The idiotypic Ab stimulated IL-4 secretion in 19 of 34 patients, IFN-gamma secretion in 26 of 34 patients, and IL-2 secretion in 25 of 34. The anti-idiotypic Ab induced IL-4 secretion in 9 of 34 patients, IFN-gamma secretion in 29 of 34 patients, and IL-2 secretion in 28 of 34 patients. These T cell responses were MHC class II-restricted. According to the cytokine-secretion patterns, Id-reactive T cells might correspond to both Th1/Th2 and/or Th0 cells. The anti-idiotypic Ab more frequently induced a Th1-type response. This study indicates that different subsets of T lymphocytes are involved in the idiotypic network in myasthenia gravis, and that these functionally different T cells may participate in the immunoregulation of the disease.
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Immunologic Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
Lefvert
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D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D009157:Myasthenia Gravis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006681:HLA-D Antigens; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma