Erschienen:
American Association for the Advancement of Science (AAAS), 2024
Erschienen in:
Science Advances, 10 (2024) 15
Sprache:
Englisch
DOI:
10.1126/sciadv.adm8841
ISSN:
2375-2548
Entstehung:
Anmerkungen:
Beschreibung:
Allograft rejection is common following clinical organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive. Calcineurin inhibitor dose escalation, corticosteroids, and/or lymphocyte depleting antibodies have remained the primary options for treatment of clinical rejection episodes. Here, we developed a highly multiplexed imaging mass cytometry panel to study the immune response in archival biopsies from 79 liver transplant (LT) recipients with either no rejection (NR), acute T cell–mediated rejection (TCMR), or chronic rejection (CR). This approach generated a spatially resolved proteomic atlas of 461,816 cells (42 phenotypes) derived from 96 pathologist-selected regions of interest. Our analysis revealed that regulatory (HLADR + T reg ) and PD1 + T cell phenotypes (CD4 + and CD8 + subsets), combined with variations in M2 macrophage polarization, were a unique signature of active TCMR. These data provide insights into the alloimmune microenvironment in clinical LT, including identification of potential targets for focused immunotherapy during rejection episodes and suggestion of a substantial role for immune exhaustion in TCMR.