Circumsporozoite protein-specific K(d)-restricted CD8+ T cells mediate protective antimalaria immunity in sporozoite-immunized MHC-I-K(d) transgenic mice.
Circumsporozoite protein-specific K(d)-restricted CD8+ T cells mediate protective antimalaria immunity in sporozoite-immunized MHC-I-K(d) transgenic mice.
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环子孢子蛋白特异性 K(d) 限制性 CD8 T 细胞在子孢子免疫的 MHC-I-K(d) 转基因小鼠中介导保护性抗疟免疫。
DOI：
10.1155/2014/728939
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发表时间：
2014
影响因子：
4.6
通讯作者：
Tsuji,Moriya
中科院分区：
文献类型：
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作者：
Huang,Jing;Tsao,Tiffany;Zhang,Min;Tsuji,Moriya
虽然CD 8 + T细胞和一种主要的红细胞前抗原环子孢子（CS）蛋白在促进辐射减毒子孢子诱导的保护性抗疟免疫中的作用已被许多研究所证实，但这些参与者在多大程度上促进抗疟免疫仍是未知的。为了解决这个问题，我们已经产生了C57 BL/6（B6）转基因（Tg）小鼠，在MHC-I启动子下表达Kd分子，称为MHC-I-Kd-Tg小鼠。在这项研究中，我们首先确定了单次免疫剂量的IrPySpz在MHC-I-Kd-Tg小鼠中诱导了显著水平的抗疟保护性免疫，但在B6小鼠中没有。然后，通过消耗体内各种T细胞亚群，我们确定了CD 8 + T细胞是IrPySpz诱导的保护性免疫的主要介质。此外，当我们将MHC-I-Kd-Tg小鼠与PyCS-转基因小鼠（CS-Tg）杂交后，用IrPySpz免疫（MHC-I-Kd-Tg × CS-Tg）F1小鼠时，我们发现IrPySpz免疫未能在（MHC-I-Kd-Tg × CS-Tg）F1小鼠中诱导保护性抗疟免疫，因此表明这些小鼠中不存在PyCS抗原依赖性免疫。这些结果表明，IrPySpz在MHC-I-Kd-Tg小鼠中诱导的保护性抗疟免疫是由CS蛋白特异性、Kd限制性CD 8 + T细胞介导的。
Although the roles of CD8+ T cells and a major preerythrocytic antigen, the circumsporozoite (CS) protein, in contributing protective antimalaria immunity induced by radiation‐attenuated sporozoites, have been shown by a number of studies, the extent to which these players contribute to antimalaria immunity is still unknown. To address this question, we have generated C57BL/6 (B6) transgenic (Tg) mice, expressing Kdmolecules under the MHC‐I promoter, called MHC‐I‐Kd‐Tg mice. In this study, we first determined that a single immunizing dose of IrPySpz induced a significant level of antimalaria protective immunity in MHC‐I‐Kd‐Tg mice but not in B6 mice. Then, by depleting various T‐cell subsetsin vivo, we determined that CD8+ T cells are the main mediator of the protective immunity induced by IrPySpz. Furthermore, when we immunized (MHC‐I‐Kd‐Tg × CS‐Tg) F1 mice with IrPySpz after crossing MHC‐I‐Kd‐Tg mice with PyCS‐transgenic mice (CS‐Tg), which are unable to mount PyCS‐specific immunity, we found that IrPySpz immunization failed to induce protective antimalaria immunity in (MHC‐I‐Kd‐Tg × CS‐Tg) F1 mice, thus indicating the absence of PyCS antigen‐dependent immunity in these mice. These results indicate that protective antimalaria immunity induced by IrPySpz in MHC‐I‐Kd‐Tg mice is mediated by CS protein‐specific, Kd‐restricted CD8+ T cells.