Dichotomous effects of latent CMV infection on the phenotype and functional properties of CD8+ T-cells and NK-cells

• There is an inverse relationship between CMV-specific NK-cell and T-cell responses.
• NKG2C+ NK-cell and CMV-specific T-cell responses are reciprocal.
• Subjects with a combined NK-cell/T-cell response or neither have high CMV IgG titers.
• High NKG2C+ NK-cell proportion is associated with high NK-cell activity (NKCA).
• Subjects with no NK-cell or T-cell response had low NKCA and few CMV-specific T-cells.

CMV markedly alters the phenotype and function of NK-cells and T-cells and has been linked to immunosenescence. We show here that subjects with effective CMV control (evidenced by low CMV IgG titers) have functional responses to CMV that are driven by either NKG2C+ NK-cells or CMV-specific T-cells (15 of 24 subjects), but not both. These data indicate that people with effective CMV control are either NK-cell or T-cell responders, and corroborates the idea that NK-cells have rheostat-like properties that regulate anti-viral T-cell responses. Whether or not lifelong CMV control through either NK-cell or T-cell responses have implications for immunosenescence remains to be determined.