IDIOTYPE-REACTIVE 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-ace tylcholine receptor and anti-idiotypic Abs. The human CD4(+) Th cells may be subdivided into different subsets according to the pattern of c ytokine production. To elucidate the subgroup of T cells involved in m yasthenia gravis, we have analyzed IL-4-, IFN-gamma-, and IL-2-secreti on patterns induced by two human disease-specific mAbs, one idiotypic and one anti-idiotypic Ab. T cells stimulated to secrete one or more o f the cytokines were found in 33 of 34 patients. The idiotypic Ab stim ulated 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 It-restricted. According to the cytokine-secr etion patterns, Id-reactive T cells might correspond to both Th1/Th2 a nd/or Th0 cells. The anti-idiotypic Ab more frequently induced a Th1-t ype response. This study indicates that different subsets of T lymphoc ytes are involved in the idiotypic network in myasthenia gravis, and t hat these functionally different T cells may participate in the immuno regulation of the disease.