Heterologous immunity in the absence of variant-specific antibodies after exposure to subpatent infection with blood-stage malaria
Heterologous immunity in the absence of variant-specific antibodies after exposure to subpatent infection with blood-stage malaria
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DOI：
10.1128/iai.73.4.2478-2485.2005
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Good, MF
中科院分区：
文献类型：
--
作者：
Elliott, SR;Kuns, RD;Good, MF
我们使用啮齿动物疟疾寄生虫查鲍迪疟原虫检测了次专利血液期疟疾(显微镜无法检测到)诱导的免疫，假设有限的感染可能允许抗原特异性T细胞的扩张，这些T细胞通常通过细胞凋亡而被删除。在3种感染药物48h治愈后，小鼠可抵抗同源或异种寄生虫(不同品系或变种)的高剂量攻击。免疫力与三种未经治疗的专利感染所产生的免疫力不同。隐性感染的小鼠缺乏针对不同表面抗原的免疫球蛋白G(IgG)，尽管产生的疟疾特异性总免疫球蛋白G效价与明显感染的小鼠相似，包括针对异源菌株之间保守的裂殖子表面抗原的抗体。攻击前采集的脾细胞在隐性感染小鼠中的抗原特异性增殖显著高于明显感染或未感染的小鼠。在隐性感染的小鼠中，淋巴细胞增殖对同种和异种寄生虫的反应相似，这表明细胞免疫的抗原靶标是保守的。在激发过程中Th1细胞因子反应明显。CD8(+)和CD4(+)淋巴细胞在潜伏感染过程中发生了细胞凋亡，提示潜伏感染后细胞免疫功能相对突出的原因之一。结论：血期疟原虫亚隐蔽感染可诱导保护性免疫，而不同于显性感染和靶向保守抗原诱导的保护性免疫。这些发现表明，基于低剂量递送多种寄生虫抗原的替代疫苗策略可以诱导针对保守决定簇的有效免疫。
We examined immunity induced by subpatent blood-stage malaria (undetectable by microscopy) using the rodent malaria parasite, Plasmodium chabaudi chabaudi, postulating that limited infection may allow expansion of antigen-specific T cells that are normally deleted by apoptosis. After three infections drug cured at 48 h, mice were protected against high-dose challenge with homologous or heterologous parasites (different strain or variant). Immunity differed from that generated by three untreated, patent infections. Subpatently infected mice lacked immunoglobulin G (IgG) to variant surface antigens, despite producing similar titers of total malaria-specific IgG to those produced by patently infected mice, including antibodies specific for merozoite surface antigens conserved between heterologous strains. Antigen-specific proliferation of splenocytes harvested prechallenge was significantly higher in subpatently infected mice than in patently infected or naive mice. In subpatently infected mice, lymphoproliferation was similar in response to homologous and heterologous parasites, suggesting that antigenic targets of cell-mediated immunity were conserved. A Th1 cytokine response was evident during challenge. Apoptosis of CD4(+) and CD8(+) splenic lymphocytes occurred during patent but not subpatent infection, suggesting a reason for the relative prominence of cell-mediated immunity after subpatent infection. In conclusion, subpatent infection with blood stage malaria parasites induced protective immunity, which differed from that induced by patent infection and targeted conserved antigens. These findings suggest that alternative vaccine strategies based on delivery of multiple parasite antigens at low dose may induce effective immunity targeting conserved determinants.