Deletion of donor‐reactive T cell clones after human liver transplant. Issue 2 (3rd October 2019)

• Record Type: Journal Article
• Authors: Savage, Thomas M.; Shonts, Brittany A.; Lau, Saiping; Obradovic, Aleksandar; Robins, Harlan; Shaked, Abraham; Shen, Yufeng; Sykes, Megan
• Is Part Of: American journal of transplantation. Volume 20:Issue 2(2020)
• Page Start: 538
• Page End: 545
• Publication Date: 2019-10-03
• Subjects: basic (laboratory) research/science -- immunobiology -- liver transplantation/hepatology -- monitoring: immune -- T cell biology -- tolerance; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15592
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : Tolerant and nontolerant patients have reduced detection of CD4 and CD8 donor‐reactive T cell clones, suggesting that partial clonal deletion of donor‐reactive T cells may be common after human liver transplantation.