A new subset of CD57+NKG2Chi NK cells is observed after HCMV infection infection (108.4)

Abstract During human cytomegalovirus (HCMV) infection, there is a preferential expansion of Natural Killer (NK) cells expressing the activating CD94-NKG2C receptor complex, implicating this receptor in the recognition of HCMV-infected cells. We recently showed that CD57+ NK cells within the CD56dimCD16+ NK cell compartment are highly mature. We hypothesized that human NK cells previously expanded in response to viruses or other pathogens will be marked by expression of CD57. Indeed, we observed in HCMV+ donors that NK cells expressing the activating NKG2C receptor are preferentially CD57+. These CD57+NKG2Chi NK cells have down-regulated the inhibitory NKG2A receptor and some inhibitory KIRs. These CD57+NKG2Chi NK cells respond better to activation through the NKG2C receptor. Furthermore, CD57+NKG2Chi NK cells expressed high amounts of LIR-1, another receptor that recognizes HCMV. Finally, in solid organ transplant recipients with symptomatic HCMV infection the percentage of CD57+NKG2Chi NK cells among the total NK cell population increased as the HCMV plasma viral load decreased. In these patients the NKG2C+ NK cells expanded and proliferated before becoming NKG2Chi and acquiring CD57 expression. Together, these results suggest that during HCMV infection, NKG2C+ NK cells expand to fight the infection, and after several divisions acquire CD57. In humans CD57 might provide a marker of "memory" or "terminally differentiated" NK cells that have been expanded in response to infection.