Involvement of CD8+ T cells in protective immunity against murine blood-stage infection with Plasmodium yoelii 17XL strain
Involvement of CD8+ T cells in protective immunity against murine blood-stage infection with Plasmodium yoelii 17XL strain
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DOI：
10.1002/eji.200939525
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发表时间：
2010-04-01
影响因子：
5.4
通讯作者：
Himeno, Kunisuke
中科院分区：
文献类型：
--
作者：
Imai, Takashi;Shen, Jianying;Himeno, Kunisuke
在开发疟疾疫苗时，最关键的一步是阐明对抗寄生虫的保护性免疫机制。我们发现，CD 8（+）T细胞有助于保护性免疫，以对抗约氏疟原虫的血液阶段寄生虫感染。用约氏疟原虫17 XL感染C57 BL/6小鼠是致命的，而用寄生虫17 XNL的低毒力菌株感染的所有小鼠获得了对约氏疟原虫17 XL的再感染的完全抗性。然而，将来自仅用约氏疟原虫17 XNL致敏的小鼠的CD 8（+）T细胞转移到宿主小鼠未能获得保护性免疫。另一方面，经辐照的宿主小鼠对约氏疟原虫17 XL感染具有完全抗性，当过继转移来自免疫小鼠的CD 8（+）T细胞时，未显示出任何等级的寄生虫血症，所述免疫小鼠在感染约氏疟原虫XNL和随后的约氏疟原虫17 XL后存活。这些来自免疫WT小鼠的保护性CD 8（+）T细胞具有产生IFN-γ、穿孔素（PFN）和颗粒酶B的潜力。当IFN-γ缺陷的小鼠被用作CD 8（+）T细胞的供体小鼠时，宿主小鼠的保护性免疫被完全废除，并且PFN缺陷小鼠的免疫被显著减弱。因此，产生IFN-γ和PFN的CD 8（+）T细胞似乎参与了对血液期疟疾感染的保护性免疫。
When developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. We found that CD8(+) T cells contribute to protective immunity against infection with blood-stage parasites of Plasmodium yoelii. Infection of C57BL/6 mice with P. yoelii 17XL was lethal, while all mice infected with a low-virulence strain of the parasite 17XNL acquired complete resistance against re-infection with P. yoelii 17XL. However, the host mice transferred with CD8(+) T cells from mice primed only with P. yoelii 17XNL failed to acquire protective immunity. On the other hand, the irradiated host mice were completely resistant to P. yoelii 17XL infection, showing no grade of parasitemia when adoptively transferred with CD8(+) T cells from immune mice that survived infection with both P. yoelii XNL and, subsequently, P. yoelii 17XL. These protective CD8(+) T cells from immune WT mice had the potential to generate IFN-gamma, perforin (PFN) and granzyme B. When mice deficient in IFN-gamma were used as donor mice for CD8(+) T cells, protective immunity in the host mice was fully abrogated, and the immunity was profoundly attenuated in PFN-deficient mice. Thus, CD8(+) T cells producing IFN-gamma and PFN appear to be involved in protective immunity against infection with blood-stage malaria.