Spatially Resolved Immune Exhaustion Within the Alloreactive Microenvironment Predicts Liver Transplant Rejection

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Apr 12

PMID 38608023

Authors

Arianna Barbetta

Brittany Rocque

Sarah Bangerth

Kelly Street

Carly Weaver

Shefali Chopra

Janet Kim

Linda Sher

Brice Gaudilliere

Omid Akbari

Rohit Kohli

Juliet Emamaullee

Affiliations

Soon will be listed here.

Abstract

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) 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.

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