Graft rejection is traditionally attributed to adaptive immune cells that recognize donor-specific alloantigens, with innate immunity having a secondary role. The finding that recipient natural killer cells are activated by the inability of graft endothelial cells to provide HLA-I-mediated inhibitory signals challenges this dogma and introduces the concept of innate rejection.
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References
Terasaki, P. I. A personal perspective: 100-year history of the humoral theory of transplantation. Transplantation 93, 751–756 (2012).
Delville, M. et al. Early acute microvascular kidney transplant rejection in the absence of anti-HLA antibodies is associated with preformed IgG antibodies against diverse glomerular endothelial cell antigens. J. Am. Soc. Nephrol. 30, 692–709 (2019).
Koenig, A. et al. Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants. Nat. Commun. 10, 5350 (2019).
Chen, C. C. et al. Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection. J. Clin. Invest. 128, 219–232 (2018).
Callemeyn, J. et al. Transcriptional changes in kidney allografts with histology of antibody-mediated rejection without anti-HLA donor-specific antibodies. J. Am. Soc. Nephrol. 31, 2168–2183 (2020).
Halloran, P. F. et al. Molecular diagnosis of ABMR with or without donor-specific antibody in kidney transplant biopsies: differences in timing and intensity but similar mechanisms and outcomes. Am. J. Transplant. 22, 1976–1991 (2022).
Hirohashi, T. et al. A novel pathway of chronic allograft rejection mediated by NK cells and alloantibody. Am. J. Transplant. 12, 313–321 (2012).
Kärre, K., Ljunggren, H. G., Piontek, G. & Kiessling, R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319, 675–678 (1986).
Uehara, S. et al. NK cells can trigger allograft vasculopathy: the role of hybrid resistance in solid organ allografts. J. Immunol. 175, 3424–3430 (2005).
Callemeyn, J. et al. Missing self-induced microvascular rejection of kidney allografts: a population-based study. J. Am. Soc. Nephrol. 32, 2070–2082 (2021).
Hamada, S., Dubois, V., Koenig, A. & Thaunat O. HLA 98, 191–199 (2021).
Dai, H. et al. Donor SIRPα polymorphism modulates the innate immune response to allogeneic grafts. Sci. Immunol. 2, eaam6202 (2017).
Dai, H. et al. PIRs mediate innate myeloid cell memory to nonself MHC molecules. Science 368, 1122–1127 (2020).
Koenig, A. et al. Missing self-induced activation of NK cells combines with non-complement-fixing donor-specific antibodies to accelerate kidney transplant loss in chronic antibody-mediated rejection. J. Am. Soc. Nephrol. 32, 479–494 (2021).
Acknowledgements
O.T. is grateful for fruitful scientific discussions and constructive insights from A. Koenig, V. Dubois, M. Naesens and F. Lakkis. His work is supported by the Etablissement Français du Sang, the Fondation pour la Recherche Médicale (PME202206015505).
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Thaunat, O. Natural killer cell-mediated innate microvascular rejection. Nat Rev Nephrol (2024). https://doi.org/10.1038/s41581-024-00862-w
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DOI: https://doi.org/10.1038/s41581-024-00862-w
