Moretto Magali, Weiss Louis M, Khan Imtiaz A
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
J Immunol. 2004 Apr 1;172(7):4402-9. doi: 10.4049/jimmunol.172.7.4402.
Encephalitozoon cuniculi continues to pose a problem for immunocompromised patients. Previous studies from our laboratory have elucidated the importance of the CD8(+) T cell subset in the protection against systemic parasite infection. There have been no studies related to the mucosal immunity induced against this orally acquired pathogen. In the present study, the immune response generated in the gut after oral E. cuniculi infection was evaluated. An early and rapid increase of the intraepithelial lymphocyte (IEL) population of orally infected animals was observed. This increase in the IEL population started as early as day 3 and peaked at day 7 postinfection with persistent elevation thereafter. At day 7 postinfection, IELs expressed strong cytokine messages (IFN-gamma and IL-10) and were highly cytotoxic for parasite-infected syngeneic macrophages. At an E:T ratio of 80:1, these cells were able to cause >60% Ag-specific target cell lysis. A significant increase in the CD8alphaalpha subset of IEL in response to an oral E. cuniculi infection was observed. To the best of our knowledge, such an early expansion of an IEL population exhibiting strong ex vivo cytotoxicity has not been reported with infectious models. These data suggest that IELs act as important barriers for multiplication of this organism leading to the successful resolution of infection. The protective role of IELs may be due both to their inflammatory (IFN-gamma production and cytotoxic response) as well as immunoregulatory (IL-10 production) properties.
兔脑炎微孢子虫继续给免疫功能低下的患者带来问题。我们实验室之前的研究已经阐明了CD8(+) T细胞亚群在抵抗全身性寄生虫感染中的重要性。尚未有关于针对这种经口感染病原体诱导的黏膜免疫的研究。在本研究中，评估了经口感染兔脑炎微孢子虫后肠道中产生的免疫反应。观察到经口感染动物的上皮内淋巴细胞（IEL）群体早期迅速增加。IEL群体的这种增加早在感染后第3天就开始了，并在感染后第7天达到峰值，此后持续升高。在感染后第7天，IEL表达强烈的细胞因子信息（IFN-γ和IL-10），并且对寄生虫感染的同基因巨噬细胞具有高度细胞毒性。在E:T比例为80:1时，这些细胞能够导致>60%的抗原特异性靶细胞裂解。观察到经口感染兔脑炎微孢子虫后IEL的CD8αα亚群显著增加。据我们所知，在感染模型中尚未报道过表现出强大体外细胞毒性的IEL群体如此早期的扩增。这些数据表明，IEL作为这种生物体增殖的重要屏障，导致感染的成功消除。IEL的保护作用可能既归因于其炎症特性（IFN-γ产生和细胞毒性反应），也归因于其免疫调节特性（IL-10产生）。
