Treatment with mTOR inhibitors after liver transplantation enables a sustained increase in regulatory T-cells while preserving their suppressive capacity.

Ghazal, Khaldoun;Stenard, Fabien;Dahlqvist, Géraldine;Barjon, Clément;Conti, Filomena;et.al.
(2018) Clinics and Research in Hepatology and Gastroenterology — Vol. 42, n° 3, p. 237-244 (2018)

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Authors
  • Ghazal, Khaldoun
    Author
  • Stenard, Fabien
    Author
  • Dahlqvist, GéraldineUCLouvain
    Author
  • Barjon, Clément
    Author
  • Conti, Filomena
    Author
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Abstract
BACKGROUND: The mammalian targets of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVR]) are used after transplantation for their immunosuppressive activity. Regulatory T-cells (Tregs) play a crucial role in immune tolerance. mTOR inhibitors appear to preserve Tregs, unlike Tacrolimus (Tac). AIM: The aim of this study was to evaluate the number and function of Tregs in liver transplant recipients before and after conversion from Tac to mTOR inhibitors. METHODS: Fifteen patients with stable graft function where converted to SRL (n=5) or EVR (n=10). Tregs (CD4+ CD25+ FoxP3+ CD127low) number and activity were analysed prospectively in blood cells using flow cytometry, and functional assay. RESULTS: Patients of both groups displayed a sustained rise in Treg levels after introduction of mTOR inhibitors (Treg levels at 3 months: 6.45±0.38% of CD4 T-cells, vs. baseline level of 3.61±0.37%, P<0.001; mean fold increase 2.04±0.73). In SRL group, 3-month Treg levels were 6.01±0.53 vs. 3.79±0.39; P=0.037, while in EVR group they were 6.63±0.67 vs. 3.54±0.51; P=0.001. By contrast, no statistical change was observed in an unconverted Tac control group. Tregs also preserved their functional ability to suppress activated T-cells. CONCLUSION: These results suggest that mTOR inhibitors induce a significant increase in Tregs while maintaining suppressive activity after LT.
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Ghazal, K., Stenard, F., Dahlqvist, G., Barjon, C., Aoudjehane, L., Scatton, O., & Conti, F. (2018). Treatment with mTOR inhibitors after liver transplantation enables a sustained increase in regulatory T-cells while preserving their suppressive capacity. Clinics and Research in Hepatology and Gastroenterology, 42(3), 237-244. https://doi.org/10.1016/j.clinre.2017.10.001 (Original work published 2018)