en
Scientific article
Open access
English

Imaging alloreactive T cells provides early warning of organ transplant rejection

Published inJCI insight, vol. 6, no. 13, e145360
Publication date2021-07-08
First online date2021-07-08
Abstract

Diagnosis of organ transplant rejection relies upon biopsy approaches to confirm alloreactive T cell infiltration in the graft. Immune molecular monitoring is under investigation to screen for rejection, though these techniques have suffered from low specificity and lack of spatial information. ImmunoPET utilizing antibodies conjugated to radioisotopes has the potential to improve early and accurate detection of graft rejection. ImmunoPET is capable of noninvasively visualizing the dynamic distribution of cells expressing specific immune markers in the entire body over time. In this work, we identify and characterize OX40 as a surrogate biomarker for alloreactive T cells in organ transplant rejection and monitor its expression by utilizing immunoPET. In a dual murine heart transplant model that has both syngeneic and allogeneic hearts engrafted in bilateral ear pinna on the recipients, OX40 immunoPET clearly depicted alloreactive T cells in the allograft and draining lymph node that were not observed in their respective isograft counterparts. OX40 immunoPET signals also reflected the subject's immunosuppression level with tacrolimus in this study. OX40 immunoPET is a promising approach that may bridge molecular monitoring and morphological assessment for improved transplant rejection diagnosis.

eng
Keywords
  • Immunology
  • Organ transplantation
  • T cells
  • Transplantation
  • Animals
  • Antigens, Differentiation / analysis
  • Biomarkers / analysis
  • Early Diagnosis
  • Gene Expression Profiling / methods
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology
  • Heart Transplantation / adverse effects
  • Humans
  • Mass Screening / methods
  • Mice
  • Monitoring, Immunologic / methods
  • OX40 Ligand / analysis
  • OX40 Ligand / immunology
  • Positron-Emission Tomography / methods
  • Radioimmunoassay / methods
  • T-Lymphocytes / immunology
Citation (ISO format)
HIRAI, Toshihito et al. Imaging alloreactive T cells provides early warning of organ transplant rejection. In: JCI insight, 2021, vol. 6, n° 13, p. e145360. doi: 10.1172/jci.insight.145360
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Article (Published version)
Identifiers
ISSN of the journal2379-3708
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