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

Am J Transplant. 2020 Feb;20(2):538-545. doi: 10.1111/ajt.15592. Epub 2019 Oct 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clonal Deletion / physiology*
  • Humans
  • Immunosuppression Therapy*
  • Liver Transplantation / adverse effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology*
  • Tissue Donors
  • Transplantation Tolerance / physiology