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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Differential induction of IgE-mediated anaphylaxis after soluble vs. cell-bound tolerogenic peptide therapy of autoimmune encephalomyelitis
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Differential induction of IgE-mediated anaphylaxis after soluble vs. cell-bound tolerogenic peptide therapy of autoimmune encephalomyelitis

机译：自身免疫性脑脊髓炎可溶性与细胞结合耐受肽治疗后IgE介导的过敏反应的差异诱导

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摘要

The ability of different forms of myelin peptides to induce tolerance for the treatment of preestablished murine experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, was evaluated. i.v. administration of myelin peptide-pulsed, ethylene carbodiimide-fixed syngeneic splenocytes, but not soluble myelin peptide monomers or oligomers, proved exceedingly effective at treating preestablished EAE, resulting in amelioration of disease progression. In addition to the lack of therapeutic efficacy of soluble peptide and peptide oligomer, administering them i.v. after the onset of clinical symptoms in many but not all peptide-induced EAE models led to a rapid-onset anaphylactic reaction characterized by respiratory distress, erythema, decreased body temperature, unresponsiveness, and, often, death. By using anti-IgE antibody treatments and mice with targeted mutations of the Fc gamma RIII alpha-chain or the common gamma-chain of Fc epsilon RI and Fc gamma RI/III, we demonstrate that IgE crosslinking of Fc epsilon RI appears to be necessary and sufficient for myelin peptide-induced anaphylaxis. The implications of these findings to myelin peptide/protein tolerance strategies for the treatment of multiple sclerosis are discussed.
机译：评估了不同形式的髓磷脂肽诱导耐受的能力，以治疗预先建立的鼠实验性自身免疫性脑脊髓炎（EAE），多发性硬化症的小鼠模型。 i.v.施用髓磷脂肽脉冲的，乙烯碳二亚胺固定的同系脾细胞而不是可溶性髓鞘肽单体或寡聚体的施用，在治疗预先建立的EAE方面极其有效，从而改善了疾病进展。除了缺乏可溶性肽和肽寡聚物的治疗功效外，静脉内施用它们。在许多但并非全部由肽诱导的EAE模型中出现临床症状后，会导致快速发作的过敏反应，其特征为呼吸窘迫，红斑，体温下降，无反应性，通常是死亡。通过使用抗IgE抗体治疗和具有FcεRRI的FcγRIIIα链或常见γ链的靶向突变的小鼠和FcγRI / III，我们证明FcεRI的IgE交联似乎是必要的并且足以用于髓磷脂肽诱导的过敏反应。讨论了这些发现对髓磷脂肽/蛋白质耐受策略治疗多发性硬化症的意义。

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