T cell-mediated rejection of kidney transplants: a personal viewpoint
- PMID: 20346061
- DOI: 10.1111/j.1600-6143.2010.03053.x
T cell-mediated rejection of kidney transplants: a personal viewpoint
Abstract
In kidney allografts, T cell mediated rejection (TCMR) is characterized by infiltration of the interstitium by T cells and macrophages, intense IFNG and TGFB effects, and epithelial deterioration. Recent experimental and clinical studies provide the basis for a provisional model for TCMR. The model proposes that the major unit of cognate recognition in TCMR is effector T cells engaging donor antigen on macrophages. This event creates the inflammatory compartment that recruits effector and effector memory CD4 and CD8 T cells, both cognate and noncognate, and macrophage precursors. Cognate T cells cross the donor microcirculation to enter the interstitium but spare the microcirculation. Local inflammation triggers dedifferentiation of the adjacent epithelium (e.g. loss of transporters and expression of embryonic genes) rather than cell death, via mechanisms that do not require known T-cell cytotoxic mechanisms or direct contact of T cells with the epithelium. Local epithelial changes trigger a response of the entire nephron and a second wave of dedifferentiation. The dedifferentiated epithelium is unable to exclude T cells, which enter to produce tubulitis lesions. Thus TCMR is a cognate recognition-based process that creates local inflammation and epithelial dedifferentiation, stereotyped nephron responses, and tubulitis, and if untreated causes irreversible nephron loss.
Similar articles
-
Donor Fas is not necessary for T-cell-mediated rejection of mouse kidney allografts.Am J Transplant. 2008 Oct;8(10):2049-55. doi: 10.1111/j.1600-6143.2008.02375.x. Am J Transplant. 2008. PMID: 18828768
-
A 2-fold Approach to Polyoma Virus (BK) Nephropathy in Kidney Transplants: Distinguishing Direct Virus Effects From Cognate T Cell-mediated Inflammation.Transplantation. 2021 Nov 1;105(11):2374-2384. doi: 10.1097/TP.0000000000003884. Transplantation. 2021. PMID: 34310102
-
Molecular landscape of T cell-mediated rejection in human kidney transplants: prominence of CTLA4 and PD ligands.Am J Transplant. 2014 Nov;14(11):2565-76. doi: 10.1111/ajt.12946. Epub 2014 Sep 12. Am J Transplant. 2014. PMID: 25219326
-
Cell mediated rejection revisited: Past, current, and future directions.Nephrology (Carlton). 2018 Jul;23 Suppl 2:45-51. doi: 10.1111/nep.13283. Nephrology (Carlton). 2018. PMID: 29968416 Review.
-
Analysis of intragraft effector mechanisms associated with human renal allograft rejection: immunohistological studies with monoclonal antibodies.Immunol Rev. 1984;77:61-84. doi: 10.1111/j.1600-065x.1984.tb00718.x. Immunol Rev. 1984. PMID: 6232203 Review.
Cited by
-
N6-methyladenosine regulators-related immune genes enable predict graft loss and discriminate T-cell mediate rejection in kidney transplantation biopsies for cause.Front Immunol. 2022 Nov 22;13:1039013. doi: 10.3389/fimmu.2022.1039013. eCollection 2022. Front Immunol. 2022. PMID: 36483557 Free PMC article.
-
Diagnosis of T-cell-mediated kidney rejection by biopsy-based proteomic biomarkers and machine learning.Front Immunol. 2023 Feb 6;14:1090373. doi: 10.3389/fimmu.2023.1090373. eCollection 2023. Front Immunol. 2023. PMID: 36814924 Free PMC article.
-
The Role of Interleukin-6 (IL-6) in the Systemic Inflammatory Response in Xenograft Recipients and in Pig Kidney Xenograft Failure.Front Immunol. 2021 Dec 8;12:788949. doi: 10.3389/fimmu.2021.788949. eCollection 2021. Front Immunol. 2021. PMID: 34956220 Free PMC article.
-
One-year Allograft and Patient Survival in Renal Transplant Recipients Receiving Antiplatelet Therapy at the Time of Transplantation.Int J Organ Transplant Med. 2018;9(1):10-19. Epub 2018 Feb 1. Int J Organ Transplant Med. 2018. PMID: 29531642 Free PMC article.
-
The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation.Front Immunol. 2020 Jul 23;11:1454. doi: 10.3389/fimmu.2020.01454. eCollection 2020. Front Immunol. 2020. PMID: 32793200 Free PMC article. Review.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical
Research Materials