TY - JOUR
T1 - Natural Killer Cells
T2 - Critical Effectors during Antibody-mediated Rejection of Solid Organ Allografts
AU - Miyairi, Satoshi
AU - Baldwin, William M.
AU - Valujskikh, Anna
AU - Fairchild, Robert L.
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Antibody-mediated rejection (AMR) is an important cause of graft loss and continues to present a formidable obstacle to successful transplantation. Unresolved problems continue to be the absence of effective strategies to ablate the donor-specific antibody (DSA) response as well as to attenuate the antibody-mediated graft tissue injury. While the properties of DSA that cause greater graft tissue injury and the characteristic microvascular pathology of the graft injury are well documented, the mechanisms underlying the injury mediated by the antibodies remains unclear. Recent transcriptome interrogation of kidney and heart biopsies procured during ongoing AMR has indicated the expression of genes associated with natural killer (NK) cell activation that is absent during T cell-mediated rejection. The expression of NK cell transcripts during AMR correlates with the presence of CD56+cells in the microcirculation inflammation observed during AMR. Several mouse models have recently demonstrated the role of NK cells in antibody-mediated chronic vasculopathy in heart allografts and the requirement for NK cell activation during acute AMR of kidney allografts. In the latter model, NK cell activation within kidney allografts is regulated by the activation of myeloid cells producing myeloperoxidase. Overall, the studies to date indicate that AMR constitutes a complex series of DSA-induced interactions with components of the innate immune response. The innate immune participants and their expressed effector functions resulting in the rejection are beginning to be identified. The identification of these components should uncover novel targets that can be used to attenuate acute graft tissue injury in the presence of DSA.
AB - Antibody-mediated rejection (AMR) is an important cause of graft loss and continues to present a formidable obstacle to successful transplantation. Unresolved problems continue to be the absence of effective strategies to ablate the donor-specific antibody (DSA) response as well as to attenuate the antibody-mediated graft tissue injury. While the properties of DSA that cause greater graft tissue injury and the characteristic microvascular pathology of the graft injury are well documented, the mechanisms underlying the injury mediated by the antibodies remains unclear. Recent transcriptome interrogation of kidney and heart biopsies procured during ongoing AMR has indicated the expression of genes associated with natural killer (NK) cell activation that is absent during T cell-mediated rejection. The expression of NK cell transcripts during AMR correlates with the presence of CD56+cells in the microcirculation inflammation observed during AMR. Several mouse models have recently demonstrated the role of NK cells in antibody-mediated chronic vasculopathy in heart allografts and the requirement for NK cell activation during acute AMR of kidney allografts. In the latter model, NK cell activation within kidney allografts is regulated by the activation of myeloid cells producing myeloperoxidase. Overall, the studies to date indicate that AMR constitutes a complex series of DSA-induced interactions with components of the innate immune response. The innate immune participants and their expressed effector functions resulting in the rejection are beginning to be identified. The identification of these components should uncover novel targets that can be used to attenuate acute graft tissue injury in the presence of DSA.
UR - http://www.scopus.com/inward/record.url?scp=85100360370&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100360370&partnerID=8YFLogxK
U2 - 10.1097/TP.0000000000003298
DO - 10.1097/TP.0000000000003298
M3 - Review article
C2 - 32384380
AN - SCOPUS:85100360370
SN - 0041-1337
SP - 284
EP - 290
JO - Transplantation
JF - Transplantation
ER -