Asymptomatic CMV infections in long‐term renal transplant recipients are associated with the loss of FcRγ from LIR‐1+ NK cells. Issue 11 (26th September 2016)

• Record Type: Journal Article
• Authors: Makwana, Nandini B.; Foley, Bree; Lee, Silvia; Fernandez, Sonia; Irish, Ashley B.; Price, Patricia
• Is Part Of: European journal of immunology. Volume 46:Issue 11(2016)
• Page Start: 2597
• Page End: 2608
• Publication Date: 2016-09-26
• Subjects: CMV -- Cytokines -- Cytotoxicity -- Natural killer cells -- Renal transplantation; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646422
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : In asymptomatic posttransplant renal transplant recipients, persistent, and active CMV expands a population of FcRγ – LIR‐1 + NKG2C – NK cells, which on cross‐linking with CMV antibody displays increased antibody dependent cell cytotoxicity, i.e. increased expression of CD107a and TNF‐α. Abstract : While it is established that cytomegalovirus (CMV) disease affects NK‐cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age‐matched controls ( n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR‐1, NKp30, NKp46, and FcRγ, a signaling adaptor molecule, on CD56 dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK‐cell function as assessed by TNF‐α and CD107a expression. The most active NK cells were FcRγ – LIR‐1 + NKG2C – and displayed high antibody‐dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom‐free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcRγ but express LIR‐1.