Beyond Histocompatibility: Donor Tissue Immune States and Their Role in Heart Transplantation
5 affiliations
- 1Cardiac Surgery and Transplantology Department, Poznan University of Medical Sciences, ½ Długa, 61-848 Poznań, Poland
- 2Thoracic Research Center, Collegium Medicum, Nicolaus Copernicus University, 85-796 Bydgoszcz, Poland
- 3Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, Italy
- 4Department of Cardiac Surgery, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior, 02-507 Warszawa, Poland
- 5Department of Research, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Specialized Therapies), 90127 Palermo, Italy
Abstract
Heart transplantation transfers not only donor alloantigens and functional myocardium but also a pre-existing tissue environment shaped by resident immune, vascular, stromal, and parenchymal populations. This review examines the hypothesis that the biological state of donor tissue influences subsequent recipient immunity and contributes to heterogeneity in allograft outcomes. Donor-resident macrophages, endothelial cells, fibroblasts, extracellular matrix, and tissue-resident lymphocytes constitute an immunologically active myocardial niche that encounters ischemia–reperfusion injury and recipient immune effectors immediately after implantation. Experimental and human studies demonstrate the dynamic coexistence and replacement of donor- and recipient-derived immune populations, with recipient cells acquiring phenotypes within the graft microenvironment. We distinguish transient donor-tissue activation from genuine tissue immune memory, which would require persistence of an exposure-induced molecular or functional state and an altered response to a subsequent challenge. Potential mechanisms include trained innate immunity, epigenetic and metabolic reprogramming, endothelial inflammatory memory, and persistent stromal–immune interactions. We propose that allograft biology be investigated at the level of the donor–recipient immune pair and outline longitudinal single-cell, spatial, and cell-of-origin approaches to test this concept in human heart transplantation.
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BibTeX
@article{urbanowicz2026beyond,
title = {{Beyond Histocompatibility: Donor Tissue Immune States and Their Role in Heart Transplantation}},
author = {Tomasz Urbanowicz and Mariusz Kowalewski and Piotr Suwalski and Giuseppe Maria Raffa},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208985},
url = {https://www.mdpi.com/1422-0067/27/20/8985},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond Histocompatibility: Donor Tissue Immune States and Their Role in Heart Transplantation
AU - Tomasz Urbanowicz
AU - Mariusz Kowalewski
AU - Piotr Suwalski
AU - Giuseppe Maria Raffa
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208985
UR - https://www.mdpi.com/1422-0067/27/20/8985
AB - Heart transplantation transfers not only donor alloantigens and functional myocardium but also a pre-existing tissue environment shaped by resident immune, vascular, stromal, and parenchymal populations. This review examines the hypothesis that the biological state of donor tissue influences subsequent recipient immunity and contributes to heterogeneity in allograft outcomes. Donor-resident macrophages, endothelial cells, fibroblasts, extracellular matrix, and tissue-resident lymphocytes constitute an immunologically active myocardial niche that encounters ischemia–reperfusion injury and recipient immune effectors immediately after implantation. Experimental and human studies demonstrate the dynamic coexistence and replacement of donor- and recipient-derived immune populations, with recipient cells acquiring phenotypes within the graft microenvironment. We distinguish transient donor-tissue activation from genuine tissue immune memory, which would require persistence of an exposure-induced molecular or functional state and an altered response to a subsequent challenge. Potential mechanisms include trained innate immunity, epigenetic and metabolic reprogramming, endothelial inflammatory memory, and persistent stromal–immune interactions. We propose that allograft biology be investigated at the level of the donor–recipient immune pair and outline longitudinal single-cell, spatial, and cell-of-origin approaches to test this concept in human heart transplantation.
SN - 1422-0067
ER -