McColl S R, Staykova M A, Wozniak A, Fordham S, Bruce J, Willenborg D O
Department of Microbiology and Immunology, University of Adelaide, Australia.
J Immunol. 1998 Dec 1;161(11):6421-6.
Emerging data suggest that polymorphonuclear leukocytes (PMNLs) can play an important role in Ag-dependent immune responses. Therefore, we have assessed the involvement of these cells in the development of an organ-specific autoimmune disease, experimental autoimmune encephalomyelitis (EAE), in the mouse. Depletion of peripheral blood PMNLs beginning day 8 after immunization significantly delayed and in some cases totally prevented the development of clinical EAE in mice. Depletion of PMNLs beginning 1 day before sensitization and continuing until day 7 postimmunization had no effect on the subsequent development of EAE, suggesting that depletion alters the efferent but not the afferent arm of the immune response. In vitro studies showed that lymphoid cells from mice protected from EAE by PMNL depletion beginning on day 8 postsensitization proliferated in response to specific Ag to a level equal to cells from sensitized animals treated with control serum, again indicating that treatment was not affecting the afferent limb of the immune response. Further evidence that PMNL may be necessary in initiating the pathology of EAE was seen in passive transfer experiments where PMNL-depleted recipients of MBP-specific lymphoid effector cells developed EAE much less effectively than did animals treated with control Ab. Taken together, these data indicate that PMNLs play a critical role in the effector phase of the development of the clinicopathologic expression of EAE in mice.
新出现的数据表明，多形核白细胞（PMNLs）在抗原依赖性免疫反应中可发挥重要作用。因此，我们评估了这些细胞在小鼠器官特异性自身免疫性疾病——实验性自身免疫性脑脊髓炎（EAE）发病过程中的作用。免疫后第8天开始清除外周血中的PMNLs，可显著延迟小鼠临床EAE的发病，在某些情况下还能完全阻止其发病。致敏前1天开始清除PMNLs并持续至免疫后第7天，对EAE的后续发展没有影响，这表明清除PMNLs改变的是免疫反应的传出臂而非传入臂。体外研究表明，从致敏后第8天开始通过清除PMNLs而免受EAE影响的小鼠的淋巴细胞，对特异性抗原的增殖反应水平与用对照血清处理的致敏动物的细胞相同，这再次表明该处理并未影响免疫反应的传入分支。在被动转移实验中可以看到更多证据，即接受髓鞘碱性蛋白（MBP）特异性淋巴细胞效应细胞但已清除PMNLs的受体发生EAE的效率远低于用对照抗体处理的动物，这表明PMNLs在引发EAE病理过程中可能是必需的。综上所述，这些数据表明PMNLs在小鼠EAE临床病理表现发展的效应阶段起关键作用。
