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Am J Transplant. 2019 Sep 11. doi: 10.1111/ajt.15592. [Epub ahead of print]

Deletion of donor-reactive T cell clones after human liver transplant.

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Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, New York.
Fred Hutchinson Cancer Research Center, Adaptive Biotechnologies, Inc., Seattle, Washington.
Division of Transplant Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, New York.
Department of Microbiology & Immunology, Columbia University Medical Center, Columbia University, New York, New York.
Department of Surgery, Columbia University Medical Center, Columbia University, New York, New York.


We recently developed a high throughput T cell receptor β chain (TCRβ) sequencing-based approach to identifying and tracking donor-reactive T cells. To address the role of clonal deletion in liver allograft tolerance, we applied this method in samples from a recent randomized study, ITN030ST, in which immunosuppression withdrawal was attempted within 2 years of liver transplantation. We identified donor-reactive T cell clones via TCRβ sequencing following a pre-transplant mixed lymphocyte reaction and tracked these clones in the circulation following transplantation in 3 tolerant and 5 non-tolerant subjects. All subjects showed a downward trend and significant reductions in donor-reactive TCRβ sequences were detected post-transplant in 6 of 8 subjects, including 2 tolerant and 4 non-tolerant recipients. Reductions in donor-reactive TCRβ sequences were greater than those of all other TCRβ sequences, including 3rd party-reactive sequences, in all 8 subjects, demonstrating an impact of the liver allograft after accounting for repertoire turnover. Although limited by patient number and heterogeneity, our results suggest that partial deletion of donor-reactive T cell clones may be a consequence of liver transplantation and does not correlate with success or failure of early immunosuppression withdrawal. These observations underscore the organ- and/or protocol-specific nature of tolerance mechanisms in humans.


T cell biology; basic (laboratory) research/science; immunobiology; liver transplantation/hepatology; monitoring: immune; tolerance


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