Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic., Australia.
Clin Exp Immunol. 2013 Sep;173(3):480-92. doi: 10.1111/cei.12132.
Natural killer T cells are a potent mediator of anti-viral immunity in mice, but little is known about the effects of manipulating NKT cells in non-human primates. We evaluated the delivery of the NKT cell ligand, α-galactosylceramide (α-GalCer), in 27 macaques by studying the effects of different dosing (1-100 μg), and delivery modes [directly intravenously (i.v.) or pulsed onto blood or peripheral blood mononuclear cells]. We found that peripheral NKT cells were depleted transiently from the periphery following α-GalCer administration across all delivery modes, particularly in doses of ≥10 μg. Furthermore, NKT cell numbers frequently remained depressed at i.v. α-GalCer doses of >10 μg. Levels of cytokine expression were also not enhanced after α-GalCer delivery to macaques. To evaluate the effects of α-GalCer administration on anti-viral immunity, we administered α-GalCer either together with live attenuated influenza virus infection or prior to simian immunodeficiency virus (SIV) infection of two macaques. There was no clear enhancement of influenza-specific T or B cell immunity following α-GalCer delivery. Further, there was no modulation of pathogenic SIVmac251 infection following α-GalCer delivery to a further two macaques in a pilot study. Accordingly, although macaque peripheral NKT cells are modulated by α-GalCer in vivo, at least for the dosing regimens tested in this study, this does not appear to have a significant impact on anti-viral immunity in macaque models.
自然杀伤 T 细胞是小鼠抗病毒免疫的有力介质，但对于操纵非人类灵长类动物中的 NKT 细胞的影响知之甚少。我们通过研究不同剂量（1-100μg）和不同给药方式[直接静脉内（i.v.）或脉冲输入血液或外周血单个核细胞]对 27 只猕猴进行了 α-半乳糖神经酰胺（α-GalCer）的递呈，评估了 NKT 细胞配体的递呈。我们发现，所有给药方式都会导致外周 NKT 细胞短暂地从外周血中耗竭，尤其是在 10μg 以上的剂量。此外，静脉内给予 α-GalCer 剂量>10μg 时，NKT 细胞数量经常持续减少。在猕猴中给予 α-GalCer 后，细胞因子表达水平也没有增强。为了评估 α-GalCer 给药对抗病毒免疫的影响，我们在活减毒流感病毒感染的同时或在猕猴感染猴免疫缺陷病毒（SIV）之前给予α-GalCer。在给予 α-GalCer 后，流感特异性 T 或 B 细胞免疫并未明显增强。进一步，在一项初步研究中，在另外两只猕猴中给予 α-GalCer 后，对致病性 SIVmac251 感染也没有调节作用。因此，尽管 α-GalCer 可以在体内调节猕猴外周血 NKT 细胞，但至少在本研究中测试的给药方案下，这似乎对猕猴模型中的抗病毒免疫没有显著影响。
