Blood-Stage Plasmodium berghei Infection Generates a Potent, Specific CD8+ T-Cell Response Despite Residence Largely in Cells Lacking MHC I Processing Machinery
Blood-Stage Plasmodium berghei Infection Generates a Potent, Specific CD8+ T-Cell Response Despite Residence Largely in Cells Lacking MHC I Processing Machinery
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DOI：
10.1093/infdis/jir656
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发表时间：
2011-12-15
影响因子：
6.4
通讯作者：
Heath, William R.
中科院分区：
文献类型：
--
作者：
Lau, Lei Shong;Ruiz, Daniel Fernandez;Heath, William R.
鼠脑型疟疾是由伯氏疟原虫ANKA感染引起的一种复杂疾病。包括CD 8（+）T细胞在内的几种细胞类型是疾病的重要效应子。尽管使用表达模型抗原的转基因寄生虫已经揭示了对这些模型抗原特异性的细胞毒性T淋巴细胞（CTL）的诱导，但没有直接证据表明对真实血液阶段寄生虫抗原的应答，也没有对其程度的任何了解。我们的研究表明，有一个显着的主要寄生虫特异性CTL反应，类似于病毒免疫，达到约30%的脾脏CD 8（+）T细胞，许多产生干扰素-γ和肿瘤坏死因子-α。这些细胞表达颗粒酶B和其他特异性应答者的标志物，具有细胞溶解性，并对广泛的主要组织相容性复合体（MHC）I限制性表位（其中5个在此鉴定）产生应答。我们的研究表明，即使病原体主要存在于缺乏MHC I加工机制的红细胞中，也可以诱导强烈的CTL应答。
Murine cerebral malaria is a complex disease caused by Plasmodium berghei ANKA infection. Several cell types, including CD8(+) T cells, are essential effectors of disease. Although the use of transgenic parasites expressing model antigens has revealed the induction of cytotoxic T lymphocytes (CTL) specific for these model antigens, there is no direct evidence for a response to authentic blood-stage parasite antigens, nor any knowledge of its magnitude. Our studies show that there is a dramatic primary parasite-specific CTL response, akin to viral immunity, reaching approximately 30% of splenic CD8(+) T cells, with many producing interferon-gamma and tumor necrosis factor-alpha. These cells express granzyme B and other markers of specific responders, are cytolytic, and respond to a broad array of major histocompatibility complex (MHC) I-restricted epitopes, 5 of which are identified here. Our studies indicate that vigorous CTL responses can be induced to pathogens even when they largely reside in red blood cells, which lack MHC I processing machinery.