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Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2Chi CD57hi NK cells gated on CD3neg CD56dim cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2Chi CD57hi NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2Chi CD57hi NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2Chi CD57hi NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.

Human Cytomegalovirus-Induced NKG2ChiCD57hiNatural Killer Cells Are Effectors Dependent on Humoral Antiviral Immunity

Human Cytomegalovirus-Induced NKG2C^hiCD57^hiNatural Killer Cells Are Effectors Dependent on Humoral Antiviral Immunity