A CD8α− subpopulation of macaque circulatory natural killer cells can mediate both antibody-dependent and antibody-independent cytotoxic activities

摘要

Natural killer (NK) cells are important components of the innate immune system that mediate effector and regulatory functions. As effector cells, NK cells help control virus-infected cells through cell-mediated antibody-dependent mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). Although macaques are an important and reliable animal model for the study of retrovirus-induced human diseases, and despite the crucial role played by NK cells in innate and adaptive immune responses against simian immunodeficiency virus (SIV), only a few studies have attempted to characterize different macaque NK cell subpopulations. In the present study, we identified a subpopulation of circulatory CD8α⁻ macaque NK cells that express NK lineage markers and exhibit cytotoxic potential. CD8α⁻ NK cells were phenotypically characterized as CD3⁻ CD14⁻ CD20⁻ CD8α⁻ cells that express NK cell markers including CD16, CD56, granzyme B, perforin, NKG2D and KIR2D. Based on their CD56/CD16 expression patterns, cells within the CD8α⁻ gate can be divided into four subpopulations: CD56^dim CD16^bright, CD56^dim CD16⁻, CD56^bright CD16⁻, and CD56⁻ CD16⁻ cells. In contrast, CD8α⁺ NK cells are 95% CD56^dim CD16^bright, which correlates with their high cytotoxic potential. Upon interleukin-15 activation, CD8α⁻ cells up-regulated CD69 expression and produced low levels of interferon-γ and tumour necrosis factor-α. Sorted CD8α⁻ NK cells were capable of killing MHC-I-devoid target cells and mediated ADCC responses against SIV gp120-coated target cells in the presence of macaque anti-gp120 antibodies. Taking into account CD8α⁻ myeloid dendritic cells, we show that about 35% of macaque CD8α⁻ cells represent a novel, functional population of circulatory NK cells that possesses cytotoxic potential and is capable of mediating anti-viral immune responses.