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A CD8α − subpopulation of macaque circulatory natural killer cells can mediate both antibody‐dependent and antibody‐independent cytotoxic activities
Author(s) -
VargasInchaustegui Diego A.,
Demberg Thorsten,
RobertGuroff Marjorie
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03493.x
Subject(s) - cytotoxic t cell , antibody , macaque , biology , immunology , cd8 , rhesus macaque , virology , immune system , genetics , neuroscience , in vitro
Summary 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.