Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection.
Arianna BarbettaBrittany RocqueSarah BangerthKelly StreetCarly WeaverShefali ChopraJanet KimLinda SherBrice L GaudilliereOmid AkbariRohit KohliJuliet A EmamaulleePublished in: Science advances (2024)
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.
Keyphrases
- single cell
- immune response
- stem cells
- peripheral blood
- high resolution
- risk assessment
- randomized controlled trial
- cell proliferation
- clinical trial
- transcription factor
- oxidative stress
- drug induced
- ultrasound guided
- photodynamic therapy
- study protocol
- extracorporeal membrane oxygenation
- human health
- big data
- dendritic cells
- electronic health record
- double blind