α-半乳糖神经酰胺激活的Vα14自然杀伤T细胞介导对小鼠疟疾的保护作用。
alpha -galactosylceramide-activated Valpha 14 natural killer T cells mediate protection against murine malaria.
作者信息
Gonzalez-Aseguinolaza G, de Oliveira C, Tomaska M, Hong S, Bruna-Romero O, Nakayama T, Taniguchi M, Bendelac A, Van Kaer L, Koezuka Y, Tsuji M
机构信息
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA.
出版信息
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8461-6. doi: 10.1073/pnas.97.15.8461.
Natural killer T (NKT) cells are a unique population of lymphocytes that coexpress a semiinvariant T cell and natural killer cell receptors, which are particularly abundant in the liver. To investigate the possible effect of these cells on the development of the liver stages of malaria parasites, a glycolipid, alpha-galactosylceramide (alpha-GalCer), known to selectively activate Valpha14 NKT cells in the context of CD1d molecules, was administered to sporozoite-inoculated mice. The administration of alpha-GalCer resulted in rapid, strong antimalaria activity, inhibiting the development of the intrahepatocytic stages of the rodent malaria parasites Plasmodium yoelii and Plasmodium berghei. The antimalaria activity mediated by alpha-GalCer is stage-specific, since the course of blood-stage-induced infection was not inhibited by administration of this glycolipid. Furthermore, it was determined that IFN-gamma is essential for the antimalaria activity mediated by the glycolipid. Taken together, our results provide the clear evidence that NKT cells can mediate protection against an intracellular microbial infection.
自然杀伤T（NKT）细胞是一类独特的淋巴细胞群体，它们共表达一种半不变的T细胞受体和自然杀伤细胞受体，在肝脏中尤为丰富。为了研究这些细胞对疟原虫肝期发育的可能影响，将一种已知在CD1d分子环境下能选择性激活Vα14 NKT细胞的糖脂α-半乳糖神经酰胺（α-GalCer）给予接种子孢子的小鼠。给予α-GalCer导致快速、强烈的抗疟活性，抑制了啮齿动物疟原虫约氏疟原虫和伯氏疟原虫肝内期的发育。α-GalCer介导的抗疟活性具有阶段特异性，因为该糖脂的给予并未抑制血期诱导感染的进程。此外，已确定干扰素-γ对于该糖脂介导的抗疟活性至关重要。综上所述，我们的结果提供了明确的证据，表明NKT细胞可介导针对细胞内微生物感染的保护作用。
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