imprint:
American Association for the Advancement of Science (AAAS), 2024
Published in:Science Advances
Language:
English
DOI:
10.1126/sciadv.adm8841
ISSN:
2375-2548
Origination:
Footnote:
Description:
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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
<jats:sup>+</jats:sup>
T
<jats:sub>reg</jats:sub>
) and PD1
<jats:sup>+</jats:sup>
T cell phenotypes (CD4
<jats:sup>+</jats:sup>
and CD8
<jats:sup>+</jats:sup>
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.
</jats:p>