title: Dual Role of Natural Killer Cells on Graft Rejection and Control of Cytomegalovirus Infection in Renal Transplantation.
abstract: Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural killer (NK) cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIRs) and graft HLA class I molecules. Several studies have addressed the impact of this variable in kidney transplant with conflicting conclusions; yet, increasing evidence supports that alloantibody-mediated NK cell activationviaFcγRIIIA (CD16) contributes to rejection. On the other hand, human cytomegalovirus (HCMV) infection constitutes a risk factor directly associated with the rate of graft loss and reduced host survival. The levels of HCMV-specific CD8+T cells have been reported to predict the risk of posttransplant infection, and KIR-B haplotypes containing activating KIR genes have been related with protection. HCMV infection promotes to a variable extent an adaptive differentiation and expansion of a subset of mature NK cells, which display the CD94/NKG2C-activating receptor. Evidence supporting that adaptive NKG2C+NK cells may contribute to control the viral infection in kidney transplant recipients has been recently obtained. The dual role of NK cells in the interrelation of HCMV infection with rejection deserves attention. Further phenotypic, functional, and genetic analyses of NK cells may provide additional insights on the pathogenesis of solid organ transplant complications, leading to the development of biomarkers with potential clinical value.
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Department of Immunology, Hospital del Mar, Barcelona, Spain; Univ. Pompeu Fabra, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
authors.affiliation: Immunogenetics-Histocompatibility, Instituto de Investigación Sanitaria Puerta de Hierro , Majadahonda , Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vilches
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Department of Nephrology, Hospital del Mar, Barcelona, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Redondo-Pachón
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM) , Barcelona , Spain.
authors.forename: Aura
authors.initials: A
authors.lastname: Muntasell
authors.affiliation: Univ. Pompeu Fabra , Barcelona , Spain.
authors.forename: Aldi
authors.initials: A
authors.lastname: Pupuleku
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Department of Immunology, Hospital del Mar, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Yélamos
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Department of Nephrology, Hospital del Mar, Barcelona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Department of Nephrology, Hospital del Mar, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Crespo
keywords: cytomegalovirus; human; natural killer; rejection; renal; transplantation