Farajnia S, Mahboudi F, Ajdari S, Reiner N E, Kariminia A, Alimohammadian M H
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Clin Exp Immunol. 2005 Mar;139(3):498-505. doi: 10.1111/j.1365-2249.2004.02702.x.
The Leishmania major amastigote class I nuclease (LmaCIN) is a developmentally regulated protein that is highly expressed in the amastigote stage of L. major. This protein is homologous to the P4 nuclease of L. pifanoi, which has been shown to induce protective immune response in a murine model. To evaluate LmaCIN as a potential human vaccine candidate, cellular immune responses to recombinant LmaCIN were examined in individuals recovered from Old World cutaneous leishmaniasis. Peripheral blood mononuclear cells (PBMC) from patients recovered from L. major infection were cultured either with recombinant LmaCIN or autoclaved L. major (ALM) as control. rLmaCIN induced significant proliferation of PBMC from 90% of recovered patients. Phenotypic analysis of proliferating cells showed that CD8(+) cells were the predominant cell type proliferating in response to rLmaC1N. Screening of culture supernatants for cytokines showed that rLmaCIN induced high levels of interferon (IFN)-gamma (mean +/- s.e.m.: 1398 +/- 179 pg/ml) associated with little interleukin (IL)-10 and little or no IL-5 production. These findings show that LmaCIN is immunogenic in humans during L. major infection and that it can elicit immunological responses relevant to immunoprophylaxis of leishmaniasis.
硕大利什曼原虫无鞭毛体I类核酸酶(LmaCIN)是一种受发育调控的蛋白质,在硕大利什曼原虫的无鞭毛体阶段高度表达。该蛋白质与皮氏利什曼原虫的P4核酸酶同源,后者已被证明在小鼠模型中可诱导保护性免疫反应。为了评估LmaCIN作为潜在的人类疫苗候选物,对从旧世界皮肤利什曼病康复的个体中针对重组LmaCIN的细胞免疫反应进行了检测。将从硕大利什曼原虫感染中康复的患者的外周血单核细胞(PBMC)与重组LmaCIN或经高压灭菌的硕大利什曼原虫(ALM)作为对照进行培养。rLmaCIN诱导了90%康复患者的PBMC显著增殖。对增殖细胞的表型分析表明,CD8(+)细胞是对rLmaC1N反应增殖的主要细胞类型。对培养上清液进行细胞因子筛选表明,rLmaCIN诱导了高水平的干扰素(IFN)-γ(平均值±标准误:1398±179 pg/ml),同时白细胞介素(IL)-10产生很少,IL-5产生很少或不产生。这些发现表明,LmaCIN在硕大利什曼原虫感染期间对人类具有免疫原性,并且它可以引发与利什曼病免疫预防相关的免疫反应。