Teitelbaum D, Arnon R, Sela M
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel 76100, USA.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3842-7. doi: 10.1073/pnas.96.7.3842.
The activity of copolymer 1 (Cop 1, Copaxone, glatiramer acetate) in suppressing experimental autoimmune encephalomyelitis (EAE) and in the treatment of multiple sclerosis patients when injected parenterally has been extensively demonstrated. In the present study we addressed the question of whether Cop 1 can induce oral tolerance to EAE similar to myelin basic protein (MBP). We now have demonstrated that oral Cop 1 inhibited EAE induction in both rats and mice. Furthermore, oral Cop 1 was more effective than oral MBP in suppressing EAE in rats. The beneficial effect of oral Cop 1 was found to be associated with specific inhibition of the proliferative and Th1 cytokine secretion responses to MBP of spleen cells from Cop 1-fed mice and rats. In all of these assays, oral Cop 1 was more effective than oral MBP. The tolerance induced by Cop 1 could be adoptively transferred with spleen cells from Cop 1-fed animals. Furthermore, Cop 1-specific T cell lines, which inhibit EAE induction in vivo, could be isolated from the above spleen cells. These T cell lines secrete the anti-inflammatory cytokines IL-10 and transforming growth factor type beta, but not IL-4, in response to both Cop 1 and MBP. In conclusion, oral Cop 1 has a beneficial effect on the development of EAE that is associated with down-regulation of T cell immune responses to MBP and is mediated by Th2/3 type regulatory cells. These results suggest that oral administration of Cop 1 may modulate multiple sclerosis as well.
共聚体1（Cop 1，考帕松，醋酸格拉替雷）经肠胃外注射时，其在抑制实验性自身免疫性脑脊髓炎（EAE）以及治疗多发性硬化症患者方面的活性已得到广泛证实。在本研究中，我们探讨了Cop 1是否能像髓鞘碱性蛋白（MBP）一样诱导对EAE的口服耐受性这一问题。我们现已证明，口服Cop 1可抑制大鼠和小鼠的EAE诱导。此外，口服Cop 1在抑制大鼠EAE方面比口服MBP更有效。发现口服Cop 1的有益作用与特异性抑制Cop 1喂养的小鼠和大鼠脾脏细胞对MBP的增殖反应及Th1细胞因子分泌反应有关。在所有这些试验中，口服Cop 1比口服MBP更有效。Cop 1诱导的耐受性可通过Cop 1喂养动物的脾脏细胞进行过继转移。此外，可从上述脾脏细胞中分离出在体内抑制EAE诱导的Cop 1特异性T细胞系。这些T细胞系在对Cop 1和MBP的反应中分泌抗炎细胞因子IL - 10和转化生长因子β型，但不分泌IL - 4。总之，口服Cop 1对EAE的发展具有有益作用，这与对MBP的T细胞免疫反应下调有关，并由Th2/3型调节细胞介导。这些结果表明，口服Cop 1也可能调节多发性硬化症。
