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Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection.
Barbetta, Arianna; Rocque, Brittany; Bangerth, Sarah; Street, Kelly; Weaver, Carly; Chopra, Shefali; Kim, Janet; Sher, Linda; Gaudilliere, Brice; Akbari, Omid; Kohli, Rohit; Emamaullee, Juliet.
Afiliação
  • Barbetta A; Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Rocque B; Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Bangerth S; Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Street K; Division of Biostatistics, Department of Population and Public Health, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Weaver C; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Chopra S; Department of Pathology, University of Southern California, Los Angeles, CA, USA.
  • Kim J; Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Sher L; Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Gaudilliere B; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Akbari O; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Kohli R; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Emamaullee J; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Sci Adv ; 10(15): eadm8841, 2024 Apr 12.
Article em En | MEDLINE | ID: mdl-38608023
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+ Treg) 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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article