Moreno-Nieves Uriel Y, Didier Céline, Lévy Yves, Barré-Sinoussi Françoise, Scott-Algara Daniel
Department of Virology, Unité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris, France.
Eur J Immunol. 2014 Aug;44(8):2370-9. doi: 10.1002/eji.201344149. Epub 2014 Jun 24.
Natural killer (NK) cells are the major antiviral effector cell population of the innate immune system. It has been demonstrated that NK-cell activity can be modulated by the interaction with dendritic cells (DCs). The HIV-1 vaccine candidate Modified Vaccinia Ankara encoding an HIV polypeptide (MVA(HIV)), developed by the French National Agency for Research on AIDS (ANRS), has the ability to prime NK cells to control HIV-1 infection in DCs. However, whether or not MVA(HIV)-primed NK cells are able to better control HIV-1 infection in CD4(+) T cells, and the mechanism underlying the specific priming, remain undetermined. In this study, we show that MVA(HIV)-primed NK cells display a greater capacity to control HIV-1 infection in autologous CD4(+) T cells. We also highlight the importance of NKG2D engagement on NK cells and DC-produced IL-15 to achieve the anti-HIV-1 specific priming, as blockade of either NKG2D or IL-15 during MVA(HIV)-priming lead to a subsequent decreased control of HIV-1 infection in autologous CD4(+) T cells. Furthermore, we show that the decreased control of HIV-1 infection in CD4(+) T cells might be due, at least in part, to the decreased expression of membrane-bound IL-15 (mbIL-15) on DCs when NKG2D is blocked during MVA(HIV)-priming of NK cells.
自然杀伤（NK）细胞是先天性免疫系统的主要抗病毒效应细胞群体。已经证明，NK细胞的活性可通过与树突状细胞（DC）的相互作用来调节。由法国国家艾滋病研究机构（ANRS）开发的编码HIV多肽的HIV-1候选疫苗安卡拉痘苗病毒（MVA(HIV)），具有启动NK细胞以控制DC中HIV-1感染的能力。然而，MVA(HIV)启动的NK细胞是否能够更好地控制CD4(+) T细胞中的HIV-1感染，以及这种特异性启动的潜在机制，仍未确定。在本研究中，我们表明MVA(HIV)启动的NK细胞在控制自体CD4(+) T细胞中的HIV-1感染方面表现出更大的能力。我们还强调了NK细胞上NKG2D的结合以及DC产生的IL-15对于实现抗HIV-1特异性启动的重要性，因为在MVA(HIV)启动过程中阻断NKG2D或IL-15会导致随后对自体CD4(+) T细胞中HIV-1感染的控制能力下降。此外，我们表明，当在NK细胞的MVA(HIV)启动过程中阻断NKG2D时，CD4(+) T细胞中HIV-1感染控制能力的下降可能至少部分归因于DC上膜结合IL-15（mbIL-15）表达的降低。
