Yuen M H, Protti M P, Diethelm-Okita B, Moiola L, Howard J F, Conti-Fine B M
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
J Immunol. 1995 Feb 1;154(3):1508-20.
CD8+ cells inhibiting the response of CD4+ cells exist in rodents, recognizing epitopes unique to a CD4+ clone (Ids) or expressed by all activated CD4+ cell (ergotypes). Stimulation of CD8+ cells recognizing ergotypes shared by all Ag-activated CD4+ cells would be useful for treatment of diseases involving undesirable CD4+ responses to ill defined Ags, such as many autoimmune diseases and allergies. As a first step toward demonstrating the existence of anti-ergotype CD8+ immunoregulatory cells in humans, we investigated here whether CD8+ cells recognizing Ag-activated CD4+ cells exist in autoimmune and healthy humans. CD4+ cells specific for human muscle acetylcholine receptor, tetanus, or diphtheria toxoids were propagated from patients with myasthenia gravis patients and healthy controls. Ag-activated CD4+ cells were irradiated and used as Ag to test the response of CD(4+)-depleted CD(8+)-enriched PBMC (CD8+ PBMC) from myasthenic patients and controls and to propagate short-term CD8+ cell lines from CD8+ PBMC. In both patients and controls CD8+ PBMC and CD8+ lines responded vigorously to autologous Ag-activated CD4+ cells. The CD8+ lines responded equally well to the Ag-activated CD4+ cells of different Ag specificity, suggesting that they recognized CD4+ ergotypes. They did not seem to respond to CD4+ cells activated by PHA. The CD8+ cells recognized class I-restricted epitopes, as their response to activated CD4+ cells was suppressed by anti-class I Ab. CD8+ cells recognizing Ag-activated CD4+ were present cells in the controls for 5 to 12 wk after immunization. In myasthenic patients, CD8+ cells recognizing activated anti-acetylcholine receptor CD4+ cells seemed to be always present.
抑制CD4+细胞反应的CD8+细胞存在于啮齿动物中，可识别CD4+克隆特有的表位（Id）或所有活化CD4+细胞表达的表位（ergotype）。刺激识别所有抗原活化CD4+细胞共有的ergotype的CD8+细胞，对于治疗涉及对不明确抗原产生不良CD4+反应的疾病（如许多自身免疫性疾病和过敏症）将是有用的。作为证明人类中存在抗ergotype CD8+免疫调节细胞的第一步，我们在此研究了自身免疫患者和健康人中是否存在识别抗原活化CD4+细胞的CD8+细胞。从重症肌无力患者和健康对照者中培养出对人肌肉乙酰胆碱受体、破伤风或白喉类毒素特异的CD4+细胞。将抗原活化的CD4+细胞进行照射，并用作抗原，以测试来自肌无力患者和对照者的CD4+缺失、CD8+富集的外周血单核细胞（CD8+ PBMC）的反应，并从CD8+ PBMC中培养短期CD8+细胞系。在患者和对照者中，CD8+ PBMC和CD8+细胞系均对自体抗原活化的CD4+细胞产生强烈反应。CD8+细胞系对不同抗原特异性的抗原活化CD4+细胞反应同样良好，表明它们识别CD4+ ergotype。它们似乎对PHA活化的CD4+细胞无反应。CD8+细胞识别I类限制性表位，因为它们对活化CD4+细胞的反应被抗I类抗体所抑制。在免疫后5至12周，识别抗原活化CD4+的CD8+细胞存在于对照者细胞中。在重症肌无力患者中，识别活化抗乙酰胆碱受体CD4+细胞的CD8+细胞似乎始终存在。
