Yi Q, Ahlberg R, Pirskanen R, Lefvert A K
Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
J Neuroimmunol. 1994 Mar;50(2):177-86. doi: 10.1016/0165-5728(94)90044-2.
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.
重症肌无力患者外周血中乙酰胆碱受体特异性T淋巴细胞的患病率很高。我们早期的研究表明，这些T淋巴细胞在自身抗原的刺激下会分泌干扰素（IFN）-γ和白细胞介素（IL）-2。根据细胞因子的产生模式，这种被刺激的T细胞可细分为不同的亚群。在本研究中，我们通过分析细胞的IL-4、IFN-γ和IL-2分泌模式来研究细胞亚群。在55%的患者中发现了自身抗原刺激的IL-4分泌，86%的患者有IFN-γ分泌，72%的患者有IL-2分泌。所有IL-2分泌增加的患者的T淋巴细胞也显示出IFN-γ分泌增加。在有或没有刺激的IFN-γ分泌的情况下都检测到了刺激的IL-4分泌。从外周血单核细胞制备物中去除单核细胞/巨噬细胞并用小鼠抗人HLA-DR抗体处理细胞后，IFN-γ和IL-4的分泌被消除。分泌IFN-γ和IL-2的T细胞数量与分泌抗乙酰胆碱受体抗体的B细胞数量之间存在正相关。我们的结果表明，乙酰胆碱受体刺激的T淋巴细胞分泌IL-4、IFN-γ和/或IL-2。这种T细胞反应受主要组织相容性复合体（MHC）II类限制且依赖单核细胞/巨噬细胞。我们的研究表明，T淋巴细胞的Th1/Th2或Th0亚群都参与了重症肌无力的自身免疫反应。
