Kemp M, Handman E, Kemp K, Ismail A, Mustafa M D, Kordofani A Y, Bendtzen K, Kharazmi A, Theander T G
Center for Medical Parasitology, Department of Clinical Microbiology, University Hospital (Rigshospitalet), University of Copenhagen, Denmark.
FEMS Immunol Med Microbiol. 1998 Mar;20(3):209-18. doi: 10.1111/j.1574-695X.1998.tb01129.x.
The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes. Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor-beta, and little interleukin-4, thereby showing a Th1 cytokine pattern. Parallel cultures showed clear Th1 and Th2 response patterns to purified protein derivative of tuberculin or tetanus toxoid, respectively. Flow cytometric analysis revealed that PSA-2 induced blastogenesis in the CD3 positive population and that these cells were the major source of interferon-gamma. The results show that Th1-like cells recognising PSA-2 are expanded during infection by L. major and that they maintain their Th1-like cytokine profile upon reactivation in vitro. Since immunity to cutaneous leishmaniasis is mediated by antigen-specific Th1-like cells, PSA-2 might be considered a vaccine candidate for human leishmaniasis.
前鞭毛体表面抗原2(PSA-2)是一种利什曼原虫寄生虫抗原,用作疫苗时可诱导Th1介导的对鼠类利什曼病的保护作用。为了评估PSA-2作为人类疫苗候选物,对皮肤利什曼病免疫个体中对PSA-2的特异性T细胞反应进行了表征。有自愈性皮肤利什曼病既往史的苏丹个体的外周血单个核细胞对从硕大利什曼原虫分离的PSA-2有强烈增殖反应,而该抗原未激活推测未接触过的丹麦人的细胞。既往有硕大利什曼原虫感染的个体的外周血单个核细胞对来自杜氏利什曼原虫前鞭毛体的PSA-2有不同的增殖反应。由硕大利什曼原虫的PSA-2激活的外周血单个核细胞产生大量干扰素-γ和肿瘤坏死因子-β,而白细胞介素-4很少,从而显示出Th1细胞因子模式。平行培养分别显示对结核菌素纯化蛋白衍生物或破伤风类毒素有明显的Th1和Th2反应模式。流式细胞术分析显示,PSA-2在CD3阳性群体中诱导细胞增殖,并且这些细胞是干扰素-γ的主要来源。结果表明,识别PSA-2的Th1样细胞在硕大利什曼原虫感染期间扩增,并且它们在体外重新激活时保持其Th1样细胞因子谱。由于对皮肤利什曼病的免疫是由抗原特异性Th1样细胞介导的,PSA-2可能被认为是人类利什曼病的疫苗候选物。