Long-Term Evolution of the Adaptive NKG2C+ NK Cell Response to Cytomegalovirus Infection in Kidney Transplantation: An Insight on the Diversity of Host–Pathogen Interaction

Human CMV infection is frequent in kidney transplant recipients (KTR). Pretransplant Ag-specific T cells and adaptive NKG2C + NK cells associate with reduced incidence of infection in CMV + KTR. Expansions of adaptive NKG2C + NK cells were reported in posttransplant CMV-infected KTR. To further explore this issue, NKG2C + NK, CD8 + , and TcRγδ T cells were analyzed pretransplant and at different time points posttransplant for ≥24 mo in a cohort of CMV + KTR ( n = 112), stratified according to CMV viremia detection. In cryopreserved samples from a subgroup ( n = 49), adaptive NKG2C + NK cell markers and T cell subsets were compared after a longer follow-up (median, 56 mo), assessing the frequencies of CMV-specific T cells and viremia at the last time point. Increased proportions of NKG2C + NK, CD8 + , and TcRγδ T cells were detected along posttransplant evolution in viremia(+) KTR. However, the individual magnitude and kinetics of the NKG2C + NK response was variable and only exceptionally detected among viremia(-) KTR, presumably reflecting subclinical viral replication events. NKG2C + expansions were independent of KLRC2 zygosity and associated with higher viral loads at diagnosis; no relation with other clinical parameters was perceived. Increased proportions of adaptive NKG2C + NK cells (CD57 + , ILT2 + , FcεRIγ - ) were observed after resolution of viremia long-term posttransplant, coinciding with increased CD8 + and Vδ2 - γδ T cells; at that stage CMV-specific T cells were comparable to viremia(-) cases. These data suggest that adaptive NKG2C + NK cells participate with T cells to restore CMV replication control, although their relative contribution cannot be discerned.