Transplantation

Oral

Increased Expression of ceacam1 in Human Orthotopic Liver Transplantation Is Cytoprotective During Ischemia-reperfusion Injury

Thursday, June 15
5:45 PM - 7:00 PM

T cell exhaustion has recently been proposed as an alternative mechanism to prevent memory development and tissue damage arising during ischemia-reperfusion injury (IRI) in murine orthotopic liver transplantation (OLT). In our cohort of human OLT patients, IRI+ recipients had more TIM-1+CD4+ and fewer TIM-3+CD4+ T cells 3 months post-transplant than IRI- recipients. Monocyte/macrophage and hepatocyte carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been identified as a key ligand for TIM-3-mediated negative immune regulation in the liver. Therefore, we sought to understand donor and recipient contributions to CEACAM1 expression in human OLT-IRI. Pre-reperfusion biopsies from IRI- recipients showed normal hepatic lateral surface CEACAM1 protein expression on bile canaliculi that was dramatically increased in post-reperfusion biopsies. This was in stark contrast to IRI+ recipients whose hepatocytes were not CEACAM1+ at either time point. Additionally, IRI+ biopsies contained larger infiltrates of myeloid cells post- vs pre-transplant; however, only myeloid cells found in IRI- biopsies expressed CEACAM1. Finally, blood from either group of recipients obtained just before reperfusion through the donor allograft increased the frequency of third party CEACAM1+ monocytes after 7 days in culture, however blood from IRI+ recipients obtained just after initial contact with the allograft induced only half the frequency of CEACAM1+ monocytes as IRI- post-reperfusion blood. These results suggest that 1) loss of hepatic CEACAM1 in the pre-transplant donor allograft contributes to IRI in OLT, and 2) increased expression of CEACAM1 in human OLT is cytoprotective during IRI, potentially regulating T cell exhaustion, thereby improving IRI-related outcome in recipients.

Rebecca A. Sosa

Postdoctoral Fellow
UCLA

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    Maura Rossetti

    UCLA

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      Ali Zarrinpar

      UCLA

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        Charles R. Lassman

        UCLA

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          Ronald W. Busuttil

          UCLA

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            David W. Gjertson

            UCLA

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              Jerzy W. Kupiec-Weglinski

              UCLA

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                Elaine F. Reed

                University of California Los Angeles

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                  Increased Expression of ceacam1 in Human Orthotopic Liver Transplantation Is Cytoprotective During Ischemia-reperfusion Injury



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