Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK‐cell subset distribution in children

Abstract

Human cytomegalovirus (HCMV) has been reported to reshape the NK-cell receptor (NKR) distribution, promoting an expansion of CD94/NKG2C(+) NK and T cells. The role of NK cells in congenital HCMV infection is ill-defined. Here we studied the expression of NKR (i.e., NKG2C, NKG2A, LILRB1, CD161) and the frequency of the NKG2C gene deletion in children with past congenital infection, both symptomatic (n = 15) and asymptomatic (n = 11), including as controls children with postnatal infection (n = 11) and noninfected (n = 20). The expansion of NKG2C(+) NK cells in HCMV-infected individuals appeared particularly marked and was associated with an increased number of LILRB1(+) NK cells in cases with symptomatic congenital infection. Increased numbers of NKG2C(+), NKG2A(+), and CD161(+) T cells were also associated to HCMV infection. The NKG2C deletion frequency was comparable in children with congenital HCMV infection and controls. Remarkably, the homozygous NKG2C(+/+) genotype appeared associated with increased absolute numbers of NKG2C(+) NK cells. Moreover, HCMV-infected NKG2C(+/+) children displayed higher absolute numbers of NKG2A(+) and total NK cells than NKG2C(+/-) individuals. Our study provides novel insights on the impact of HCMV infection on the homeostasis of the NK-cell compartment in children, revealing a modulatory influence of NKG2C copy number.