Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients

Ataya Fernández, Michelle, 1993-; Redondo Pachón, María Dolores; Llinàs-Mallol, Laura; Yélamos López, José; Heredia, Gemma; Pérez-Sáez, María José; Vila, Joan; Costa García, Marcel, 1989-; Raïch-Regué, Dàlia; Vilches, Carlos; Pascual, Julio (Pascual Santos); Crespo Barrio, Marta; López-Botet, M. (Miguel)

doi:http://dx.doi.org/10.1111/ajt.15658

Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients

Citation

Ataya M, Redondo-Pachón D, Llinàs-Mallol L, Yélamos J, Heredia G, Pérez-Sáez MJ, Vila J, Costa-García M, Raïch-Regué D, Vilches C, Pascual J, Crespo M, López-Botet M. Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients. Am J Transplant. 2020; 20(3):663-76. DOI: 10.1111/ajt.15658

Abstract

Cytomegalovirus (CMV) infection constitutes a complication for kidney transplant recipients (KTR) and CMV-specific T cells reduce the risk of viral replication in seropositive patients. CMV promotes the adaptive differentiation and expansion of an NK cell subset, hallmarked by expression of the CD94/NKG2C receptor with additional characteristic features. We previously reported an association of pretransplant NKG2C+ NK cells with a reduced incidence of CMV infection. We have strengthened the analysis in cryopreserved peripheral blood mononuclear cells from an enlarged KTR cohort (n = 145) with homogeneous immunosuppression, excluding cases at low risk of infection (ie, CMV D-R-) or receiving antiviral prophylaxis. Moreover, adaptive NKG2C+ NK cell-associated markers (ie, NKG2A, CD57, Immunoglobulin-like transcript 2 [LIR1 or LILRB1], FcεRI γ chain, and Prolymphocytic Leukemia Zinc Finger transcription factor) as well as T lymphocyte subsets were assessed by multicolor flow cytometry. The relation of NKG2C+ NK cells with T cells specific for CMV antigens was analyzed in pretransplant patients (n = 29) and healthy controls (n = 28). Multivariate Cox regression and Kaplan-Meier analyses supported that NKG2C+ NK cells bearing adaptive markers were specifically associated with a reduced incidence of posttransplant symptomatic CMV infection; no correlation between NKG2C+ NK cells and CMV-specific T cells was observed. These results support that adaptive NKG2C+ NK cells contribute to control CMV infection in KTR.