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Imaging alloreactive T cells provides early warning of organ transplant rejection
Toshihito Hirai, … , Robert S. Negrin, Sanjiv S. Gambhir
Toshihito Hirai, … , Robert S. Negrin, Sanjiv S. Gambhir
Published July 8, 2021
Citation Information: JCI Insight. ;6(13):e145360. https://doi.org/10.1172/jci.insight.145360.
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Resource and Technical Advance Immunology Transplantation

Imaging alloreactive T cells provides early warning of organ transplant rejection

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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.

Authors

Toshihito Hirai, Aaron T. Mayer, Tomomi W. Nobashi, Po-Yu Lin, Zunyu Xiao, Tomokatsu Udagawa, Kinya Seo, Federico Simonetta, Jeanette Baker, Alan G. Cheng, Robert S. Negrin, Sanjiv S. Gambhir

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Figure 1

T cell infiltration precedes loss in allograft viability in organ transplant recipients.

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T cell infiltration precedes loss in allograft viability in organ transp...
(A) Photographs of transplanted cardiac ear pinna iso (top) and allografts (bottom) at days 6 (d6), d9, and d12 after transplantation. (B and C) Electrocardiogram (ECG) of transplanted heart measured from electrodes placed on edge of iso (B) and allograft (C). Scale bars: 2 seconds. (D) Bioluminescent images depicting graft viability at d6, d9, and d12 after transplantation in a WT BALB/c mouse. Left ear; BALB/c cardiac isograft expressing firefly luciferase (FL). Right ear; C57BL/6 cardiac allograft expressing FL. Scale bar represents total flux (photon /second); red, high; blue, low. Images are representative of 9 dual graft recipient mice from 2 independent experiments. (E) Violin plot of total flux measured from cardiac allografts (n = 9) and isografts (n = 9) at each respective time point indicated on x axis. Purple, allograft (Allo); Orange, isograft (Iso). Dashed line indicates mean. **P = 0.0028 calculated by Mann-Whitney U test. (F) Images of H&E staining of allograft (top) and isograft (bottom) on d9 after transplantation. Inset box 1, skin surface region; mononuclear cell infiltration was shown in both allo- and isograft surface. Inset box 2, graft parenchyma. Massive mononuclear cell infiltration was shown in allograft parenchyma. (G) Images of immunofluorescent staining for CD3 (Green) and DAPI (Blue). Left; low magnification, right; high magnification of inset region. CD3+ T cells infiltrating allograft parenchyma.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

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