Mokhtarian F, Pino M, Ofosu-Appiah W, Grob D
Department of Medicine, Maimonides Medical Center, Brooklyn, New York.
J Clin Invest. 1990 Dec;86(6):2099-108. doi: 10.1172/JCI114948.
A study of cell surface phenotypes of PBL of myasthenia gravis (MG) patients showed that their T cells had a significantly higher percentage of 4B4+ T cells (the helper/inducer subset) than age- and sex-matched controls. The PBL of MG patients proliferated significantly higher than those of normal subjects (NS) in response to the purified alpha chain of the acetylcholine receptor (AChR). Anti-AChR antibody was present in sera of 88% of MG and none of the NS. The PBL B cells from MG only, when cultured with autologous T cells and stimulated with either pokeweed mitogen (69%), or AChR-alpha chain (38%), secreted antibody to AChR-alpha chain, whereas T and B cells alone secreted no antibody. T cells from PBL of MG patients were more readily cloned than T cells of NS, by limiting dilution, in the presence of recombinant IL-2 and in the absence of AChR-alpha chain. About 50% of T cell clones from MG patients, compared to none from NS, proliferated to AChR-alpha chain. This response was HLA-DR restricted. MG T cell clones did not display significant cytotoxic activity, as compared to control T cell clones. Our results indicate that in MG, 4B4+ regulatory T cells play their role in the pathogenesis of MG, not by cytotoxicity, but more likely by their ability to stimulate specific antibody production by B cells.
一项对重症肌无力(MG)患者外周血淋巴细胞(PBL)细胞表面表型的研究表明,与年龄和性别匹配的对照组相比,他们的T细胞中4B4 + T细胞(辅助/诱导亚群)的百分比显著更高。MG患者的PBL对乙酰胆碱受体(AChR)的纯化α链的增殖反应明显高于正常受试者(NS)。88%的MG患者血清中存在抗AChR抗体,而NS患者血清中均未检测到。仅MG患者的PBL B细胞,在与自体T细胞共培养并用美洲商陆有丝分裂原(69%)或AChR-α链(38%)刺激时,会分泌抗AChR-α链抗体,而单独的T细胞和B细胞不分泌抗体。在重组白细胞介素-2存在且无AChR-α链的情况下,通过有限稀释法,MG患者PBL中的T细胞比NS患者的T细胞更容易克隆。与NS患者的T细胞克隆无一增殖至AChR-α链相比,MG患者约50%的T细胞克隆对AChR-α链有增殖反应。这种反应受HLA-DR限制。与对照T细胞克隆相比,MG T细胞克隆未显示出明显的细胞毒性活性。我们的结果表明,在MG中,4B4 +调节性T细胞在MG发病机制中发挥作用,不是通过细胞毒性,而是更可能通过其刺激B细胞产生特异性抗体的能力。