Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis
Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis
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DOI：
10.1073/pnas.94.20.10821
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发表时间：
1997-09-30
影响因子：
11.1
通讯作者：
Arnon, R
中科院分区：
文献类型：
--
作者：
Aharoni, R;Teitelbaum, D;Arnon, R
为了进一步了解Cop 1对实验性自身免疫性脑脊髓炎(EAE)的抑制作用，我们研究了Cop 1诱导的各种T细胞株和克隆的细胞因子分泌谱，与髓鞘碱性蛋白(MBP)诱导的T细胞株不同，Cop 1诱导的T细胞株/克隆分泌Th1或Th1和Th2两种细胞因子，Cop 1诱导的T细胞株/克隆向Th2途径逐渐两极化发展，直到完全失去分泌Th1细胞因子的能力。我们的结果表明，Cop 1诱导的T细胞的极化不是免疫载体或体外生长条件的结果，而是Cop 1优先诱导Th2反应的倾向所致。所有Cop 1特异性株/克隆的反应都局限于BALB/c亲本单倍型，即使Cop 1诱导的T细胞没有暴露于自身抗原MBP，它们也通过分泌IL-4、IL-6和IL-10与MBP发生交叉反应。体内注射这些T细胞可抑制小鼠全脊髓匀浆诱导的EAE，其中可能涉及多种自身抗原，Cop-1诱导的抑制性细胞分泌抗炎细胞因子对Cop-1或MBP的反应可能解释了Cop-1对EAE和多发性硬化的治疗作用。
The synthetic amino acid copolymer copolymer 1 (Cop 1) suppresses experimental autoimmune encephalomyelitis (EAE) and is beneficial in multiple sclerosis, To further understand Cop 1 suppressive activity, we studied the cytokine secretion profile of various Cop 1-induced T cell lines and clones, Unlike T cell lines induced by myelin basic protein (MBP), which secreted either T cell helper type 1 (Th1) or both Th1 and Th2 cytokines, the T cell lines/clones induced by Cop 1 showed a progressively polarized development toward the Th2 pathway, until they completely lost the ability to secrete Th1 cytokines, Our findings indicate that the polarization of the Cop 1-induced lines did not result from the immunization vehicle or the in vitro growing conditions, but rather from the tendency of Cop 1 to preferentially induce a Th2 response, The response of all of the Cop 1 specific lines/clones, which were originated in the (SJL/J x BALB/c)F-1 hybrids, was restricted to the BALB/c parental haplotype, Even though the Cop 1-induced T cells had not been exposed to the autoantigen MBP, they crossreacted with MBP by secretion of interleukin (IL)-4, IL-6, and IL-10. Administration of these T cells in vivo resulted in suppression of EAE induced by whole mouse spinal cord homogenate, in which several autoantigens may be involved, Secretion of anti-inflammatory cytokines by Cop 1-induced suppressor cells, in response to either Cop 1 or MBP, may explain the therapeutic effect of Cop 1 in EAE and in multiple sclerosis.