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-γ 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-γ-, 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-γ 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-γ 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.