Benson J M, Stuckman S S, Cox K L, Wardrop R M, Gienapp I E, Cross A H, Trotter J L, Whitacre C C
Department of Medical Microbiology and Immunology, Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA.
J Immunol. 1999 May 15;162(10):6247-54.
Oral administration of a myelin component, myelin basic protein (MBP), induces immunological unresponsiveness to CNS Ags and ameliorates murine relapsing experimental autoimmune encephalomyelitis (REAE). However, a recent clinical trial in which multiple sclerosis patients were treated with repeated doses of oral myelin was unsuccessful in reducing disease exacerbations. Therefore, we directly compared the tolerizing capacity of myelin vs MBP during REAE in B10.PL mice. Oral administration of high doses of myelin, either before disease induction or during REAE, did not provide protection from disease or decrease in vitro T cell responses. In contrast, repeated oral administration of high doses of MBP suppressed established disease and MBP-specific T cell proliferation and cytokine responses. The frequency of IL-2-, IFN-gamma-, and IL-5-secreting MBP-specific T cells declined with MBP feeding, implicating anergy and/or deletion as the mechanism(s) of oral tolerance after high Ag doses. We have previously shown that the dosage and timing of Ag administration are critical parameters in oral tolerance induction. Studies presented here demonstrate that Ag homogeneity is also important, i.e., homogeneous Ag (MBP) is more effective at inducing oral tolerance than heterogeneous Ag (myelin).
口服髓磷脂成分髓磷脂碱性蛋白（MBP）可诱导对中枢神经系统抗原的免疫无反应性，并改善小鼠复发性实验性自身免疫性脑脊髓炎（REAE）。然而，最近一项针对多发性硬化症患者的临床试验中，多次口服髓磷脂并未成功减少疾病发作。因此，我们在B10.PL小鼠的REAE过程中直接比较了髓磷脂与MBP的免疫耐受能力。在疾病诱导前或REAE期间口服高剂量的髓磷脂，均不能预防疾病或降低体外T细胞反应。相比之下，多次口服高剂量的MBP可抑制已建立的疾病以及MBP特异性T细胞增殖和细胞因子反应。随着MBP喂养，分泌IL-2、IFN-γ和IL-5的MBP特异性T细胞频率下降，这表明高抗原剂量后口服耐受的机制是无反应性和/或细胞缺失。我们之前已经表明，抗原给药的剂量和时间是诱导口服耐受的关键参数。此处呈现的研究表明，抗原同质性也很重要，即同质抗原（MBP）比异质抗原（髓磷脂）更有效地诱导口服耐受。
