Regulation in maintenance of remission involving the prognosis of a model of Multiple Sclerosis

用几种脑源性髓磷脂多肽免疫SJL/J小鼠可引起实验性自身免疫性脑脊髓炎(EAE)，与多发性硬化症(MS)相似。通过对PLP136-150单相性EAE和PLP139-151复发性EAE的研究，我们发现维持EAE缓解的非遗传因素如下：A)致脑多肽本身的层级，即具有发生急性EAE能力的优势肽越多，复发和再诱导的发生率越低；B)缓解期在淋巴结中诱导的CD4^+CD25^+调节性T细胞(Treg)，其特点是维持在高水平，并含有同时表达CD69和CD103的高效Treg(=DP-Treg)。这种DP-Treg由于IL-6R的低表达而保留了Treg的特性，但它与EAE和MS的病原体Th17有一些相似之处，可能在某些情况下具有调节功能，而且即使在非炎症条件下也可以观察到这种调节作用，这表明一种有效和安全的自身免疫疫苗的可能性。

Immunization with several encephalitogenic myelin peptides causes experimental autoimmune encephalomyelitis (EAE), resembling variety types of multiple sclerosis (MS).Noting that immunizing SJL/J mice with overlapping myelin proteolipid protein (PLP) residues 136-150 and 139-151 could induce quite different diseases ; monophasic EAE by PLP136-150 and relapsing EAE by PLP139-151, we found the non-genetic factors to maintain remission of EAE as follows : A) the hierarchy of the encephalitogenic peptide itself, which means that the more dominant peptide possessed the capacity to develop acute EAE, the less relapse and re-induction of EAE were occurred, and B) CD4^+CD25^+ regulatory T cells (Treg) induced in the lymphnodes during remission phase, which is characterized by maintenance at high level and by content of the highly potent Treg expressing both CD69 and CD103 (=DP-Treg). This DP-Treg can keep the property of Treg due to the low expression of IL-6R, nevertheless it shares some signatures with Th17, a pathogenic cause of EAE and MS, and may conduct regulatory function in situ.Furthermore, such regulation could be observed even under non-inflammatory condition, indicating the possibility of a potent and a safe autoimmune vaccination.