Vargas-Inchaustegui Diego A, Ying Olivia, Demberg Thorsten, Robert-Guroff Marjorie
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA.
Front Immunol. 2016 Aug 31;7:340. doi: 10.3389/fimmu.2016.00340. eCollection 2016.
NK cells are crucial components of the innate immune system due to their capacity to exert rapid cytotoxic and immunomodulatory function in the absence of prior sensitization. NK cells can become activated by exposure to target cells and/or by cytokines produced by antigen-presenting cells. In this study, we examined the effects of a simian immunodeficiency virus (SIV) vaccine regimen and subsequent SIV infection on the cytotoxic and immunomodulatory functions of circulatory NK cells. While vaccination did not significantly impact the capacity of NK cells to kill MHC-devoid 721.221 target cells, SIV-infection led to a significant decrease in target cell killing. NK cells from uninfected macaques were responsive to a low dose (5 ng/ml) of IL-15 pre-activation, leading to significant increases in their cytotoxic potential, however, NK cells from SIV-infected macaques required a higher dose (50 ng/ml) of IL-15 pre-activation in order to significantly increase their cytotoxic potential. By contrast, no differences were observed in the capacity of NK cells from vaccinated and SIV-infected macaques to respond to IL-12 and IL-18. Similarly, NK cells both before and after infection exhibited equivalent responses to Fc-mediated activation. Collectively, our results show that early SIV-infection impairs the natural cytotoxic capacity of circulatory NK cells without affecting Fc-mediated or cytokine-producing function.
自然杀伤细胞（NK细胞）是先天免疫系统的关键组成部分，因为它们能够在未预先致敏的情况下迅速发挥细胞毒性和免疫调节功能。NK细胞可通过接触靶细胞和/或抗原呈递细胞产生的细胞因子而被激活。在本研究中，我们检测了猿猴免疫缺陷病毒（SIV）疫苗接种方案及随后的SIV感染对循环NK细胞的细胞毒性和免疫调节功能的影响。虽然疫苗接种对NK细胞杀伤缺乏主要组织相容性复合体（MHC）的721.221靶细胞的能力没有显著影响，但SIV感染导致靶细胞杀伤能力显著下降。未感染猕猴的NK细胞对低剂量（5 ng/ml）的白细胞介素-15（IL-15）预激活有反应，导致其细胞毒性潜力显著增加，然而，来自SIV感染猕猴的NK细胞需要更高剂量（50 ng/ml）的IL-15预激活才能显著增加其细胞毒性潜力。相比之下，接种疫苗和SIV感染猕猴的NK细胞对IL-12和IL-18反应的能力没有差异。同样，感染前后的NK细胞对Fc介导的激活表现出相同的反应。总体而言，我们的结果表明，早期SIV感染会损害循环NK细胞的天然细胞毒性能力，而不影响Fc介导的或产生细胞因子的功能。
