Allorecognition by recipient NK cells: Molecular mechanisms and role in chronic vascular rejection

Introduction. -The dogma in transplant immunology defends the concept that allograft rejection is initiated exclusively by the adaptive immune system of the recipient, which is the only one capable of recognizing the donor's specific alloantigens (allorecognition phenomenon). Results. - In this model, the cells of innate immunity in general (and the NK cells in particular), are only downstream effectors, which only participate in the destruction of the graft when they are recruited by adaptive effectors: alloreactive T cells or donor specific antibodies (DSA). Challenging this view, recent data from our team has demonstrated that recipient NK cells are capable of allorecognition because they can detect the absence of HLA class I molecules on the surface of graft endothelial cells: a situation called "missing self". The "missing self" triggers NK cell-dependent activation of the mTORC1 signaling pathway responsible for microvascular inflammation, which leads to the development of chronic "innate" vascular rejection that negatively impacts graft survival. Conclusion. - Highlighting the critical role of NK cells in chronic vascular rejection is crucial and suggests that therapies targeting NK cell activation mechanisms may be effective in patients. (C) 2022 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.