The role of mast cells in the elicitation of experimental allergic encephalomyelitis.
The role of mast cells in the elicitation of experimental allergic encephalomyelitis.
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DOI：
10.4049/jimmunol.142.5.1476
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发表时间：
1989-03
影响因子：
4.4
通讯作者：
G. Dietsch;D. Hinrichs
中科院分区：
文献类型：
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作者：
G. Dietsch;D. Hinrichs
实验性变态反应性脑脊髓炎（EAE）是一种T细胞介导的自身免疫性疾病，可以通过主动免疫大鼠的淋巴细胞转移到幼稚受体。在小鼠中，先前的研究表明组胺/5-羟色胺在活动性EAE的发展中起作用。我们已经发现，髓鞘碱性蛋白反应性细胞转移一个双相的皮肤试验反应的幼稚大鼠类似于已经描述的小鼠接触性皮炎系统，其中肥大细胞致敏的Ag特异性T细胞因子是必需的皮肤试验反应的诱导。用5-羟色胺受体拮抗剂赛庚啶或麦角新碱治疗细胞受体，阻断或显著减少EAE的发展。此外，发现当在细胞转移后第3天至第6天施用时，赛庚啶治疗在阻断临床疾病方面是有效的。与此相反，赛庚啶治疗诱导麻痹前0至3天，未能改变临床疾病的过程。还发现肥大细胞脱粒的抑制剂阿替克罗米有效地阻断过继转移的EAE的诱发，并且还发现在临床疾病发作之前施用时有效。利血平是一种已知的化合物，通过迫使颗粒内容物进入细胞质，在细胞质中被细胞酶降解，从而消耗肥大细胞的血管活性胺，也可有效阻断活性和过继转移的EAE。疾病抑制被认为是部分逆转与帕吉林，单胺氧化酶的抑制剂。此外，来自治疗动物的淋巴细胞能够将疾病转移至初始受体，并且除了IL-2产生之外，如通过Ag或有丝分裂原驱动的增殖所评估的，似乎具有正常活性。
Experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease can be transferred with lymphoid cells from actively immunized rats into naive recipients. In the mouse, previous studies have suggested a role for histamine/serotonin in the development of active EAE. We have found that myelin basic protein-reactive cells transfer a biphasic skin test response to naive rats analogous to what has been described in the mouse contact dermatitis system, where mast cell sensitization by Ag-specific T cell factors is required for the induction of skin test responses. Treatment of cell recipients with the serotonin receptor antagonists, cyproheptadine or methysergide, blocked or significantly reduced the development of EAE. Furthermore, it was found that treatment with cyproheptadine was effective in blocking clinical disease when administered day 3 to day 6 after cell transfer. In contrast, cyproheptadine treatments before induction of paralysis day 0 to 3, failed to alter the course of clinical disease. The inhibitor of mast cell degranulation, proxicromil, was also found to effectively block the elicitation of adoptively transferred EAE and was also found to be effective when administered just before the onset of clinical disease. Reserpine, a compound known to deplete mast cells of vasoactive amines by forcing granule contents into the cytoplasm where they are degraded by cell enzymes, was also effective in blocking both active and adoptively transferred EAE. Disease inhibition was found to be partially reversed with pargyline, an inhibitor of monoamine oxidase. In addition lymphocytes from treated animals were capable of transferring disease to naive recipients and appeared to have normal activity as assessed by Ag-or mitogen-driven proliferation in addition to IL-2 production.