Reeves R Keith, Li Haiying, Jost Stephanie, Blass Eryn, Li Hualin, Schafer Jamie L, Varner Valerie, Manickam Cordelia, Eslamizar Leila, Altfeld Marcus, von Andrian Ulrich H, Barouch Dan H
1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. [2] Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge, Massachusetts, USA.
Nat Immunol. 2015 Sep;16(9):927-32. doi: 10.1038/ni.3227. Epub 2015 Jul 20.
Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in mouse NK cells. However, it has remained unclear whether this phenomenon also exists in primates. We found that splenic and hepatic NK cells from SHIV(SF162P3)-infected and SIV(mac251)-infected macaques specifically lysed Gag- and Env-pulsed dendritic cells in an NKG2-dependent fashion, in contrast to NK cells from uninfected macaques. Moreover, splenic and hepatic NK cells from Ad26-vaccinated macaques efficiently lysed antigen-matched but not antigen-mismatched targets 5 years after vaccination. These data demonstrate that robust, durable, antigen-specific NK cell memory can be induced in primates after both infection and vaccination, and this finding could be important for the development of vaccines against HIV-1 and other pathogens.
自然杀伤(NK)细胞传统上被认为是固有免疫的非特异性组成部分,但最近的研究表明小鼠NK细胞具有抗原特异性记忆的特征。然而,这种现象在灵长类动物中是否也存在仍不清楚。我们发现,与未感染猕猴的NK细胞相比,感染SHIV(SF162P3)和SIV(mac251)的猕猴的脾脏和肝脏NK细胞以NKG2依赖的方式特异性裂解Gag和Env脉冲树突状细胞。此外,接种Ad26疫苗的猕猴的脾脏和肝脏NK细胞在接种5年后能有效裂解抗原匹配而非抗原不匹配的靶标。这些数据表明,感染和接种疫苗后均可在灵长类动物中诱导出强大、持久的抗原特异性NK细胞记忆,这一发现对于开发抗HIV-1和其他病原体的疫苗可能具有重要意义。