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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.

Author information

1
Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, New York.
2
Fred Hutchinson Cancer Research Center, Adaptive Biotechnologies, Inc., Seattle, Washington.
3
Division of Transplant Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
4
Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, New York.
5
Department of Microbiology & Immunology, Columbia University Medical Center, Columbia University, New York, New York.
6
Department of Surgery, Columbia University Medical Center, Columbia University, New York, New York.

Abstract

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.

KEYWORDS:

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

PMID:
31509321
DOI:
10.1111/ajt.15592

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