The Role of Killer Cell Immunoglobulin-Like Receptors (KIR) Expressed By Natural Killer Cells During Acute CMV Infection After Kidney Transplantation.

Abstract

A. Human cytomegalovirus (CMV) infection may be a serious condition after solid organ transplantation. Natural killer (NK) cells are not affected by immunosuppressive drugs and played a critical role to control viral infection. The regulation of NK cells depends on a large range of activating and inhibitory receptors, such as the family of killer-cell immunoglobulin-like receptors (KIR). The respective activities of the different KIR proteins expressed by NK cells during CMV infection have not been extensively studied, B. We analyzed the expression of KIR in a cohort of 22 CMV IgG+ renal transplant patients at the time of CMV reactivation, after antiviral therapy and 6 months later. We set up an in vitro model in which NK cells, isolated from healthy donors or from transplanted patients, target allogeneic CMV infected or not infected fibroblasts. C. Our data revealed a marked expression of KIR3DL1 during the acute phase of the reactivation. We demonstrate a significant correlation between the lysis of CMV-infected fibroblasts and the expression of KIR3DL1 receptor. Blocking experiments with anti-MHC-I, but also anti-NKG2D and anti-NKG2C antibodies confirmed the importance of KIR3DL1. D. In addition to the C-type lectin receptors NKG2C and NKG2D, our results suggest that KIR proteins and especially KIR3DL1, play an important role in the elimination of CMV- infected cells in immunosuppressed patients.