Epicutaneous immunization with autoantigenic peptides induces T suppressor cells that prevent experimental allergic encephalomyelitis
Epicutaneous immunization with autoantigenic peptides induces T suppressor cells that prevent experimental allergic encephalomyelitis
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DOI：
10.1016/s1074-7613(03)00239-5
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发表时间：
2003-09-01
期刊：
影响因子：
32.4
通讯作者：
Janeway, CA
中科院分区：
文献类型：
--
作者：
Bynoe, MS;Evans, JT;Janeway, CA
关于抑制性/调节性T细胞如何在体内直接产生并防止自身免疫的信息仍然是零碎的。我们在这里表明，表皮免疫（ECi）与髓鞘碱性蛋白（MBP），Ac 1 -11的免疫优势肽，保护小鼠转基因的Ac 1 -11特异性T细胞受体对诱导和自发形式的实验性过敏性脑脊髓炎（EAE）。这种保护作用是抗原特异性和抗原剂量依赖性的，并且由CD 4（+）/CD 25（-）T细胞介导，其抑制活性需要细胞-细胞接触，并且可以将保护作用转移到幼稚受体。这些ECi诱导的抑制性T细胞通过抑制幼稚MBP特异性CD 4 T细胞的活化及其分泌IFN-γ的能力来控制幼稚MBP特异性CD 4 T细胞。受保护小鼠脑内无CD 4 T细胞浸润。最后，ECi与自身抗原肽保护两个非转基因模型从复发缓解型EAE的抗原特异性和抗原剂量依赖性的方式。
Information on how suppressor/regulatory T cells can be generated directly in vivo and prevent autoimmunity remains fragmentary. We show here that epicutaneous immunization (ECi) with the immunodominant peptide of myelin basic protein (MBP), Ac1-11, protects mice that are transgenic for an Ac1-11-specific T cell receptor against both the induced and spontaneous forms of experimental allergic encephalomyelitis (EAE). This protection was antigen specific and antigen dose dependent, and was mediated by CD4(+)/CD25(-) T cells whose suppressive activity required cell-cell contact and could transfer protection to naive recipients. These ECi-induced suppressor T cells controlled naive MBP-specific CD4 T cells by inhibiting both their activation and their capacity to secrete IFN-gamma. There was no CD4 T cell infiltration in the brain of protected mice. Finally, ECi with autoantigenic peptides protected two nontransgenic models from relapsing-remitting EAE in an antigen-specific and antigen dose-dependent manner.