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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 4

The clinical immunosuppressant tacrolimus reduces OX40 alloreactive T cell numbers and prevents allograft rejection.

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The clinical immunosuppressant tacrolimus reduces OX40 alloreactive T ce...
(A) Top: tacrolimus (Fk) immunosuppressant treatment schedule following cardiac ear pinna allograft transplantation. Bottom: quantification of the number of OX40+ CD4 T cells in the allograft, allo-draining, and non-allo-draining cervical lymph node (CLN) for allograft recipients treated with immunosuppressant (Fk) or vehicle (PBS) at d9 after transplantation. (B) Images of H&E staining depicting cellular infiltrate in allografts of immunosuppressed (Fk) or vehicle-treated mice (PBS) at d9. Boxes 1 and 2 are zoomed-in regions of the indicated insets. Box 1, graft surface; box 2, graft parenchyma.

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