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

Clin Res Hepatol Gastroenterol 2018 06 23;42(3):237-244. Epub 2017 Nov 23.

Sorbonne universités, UPMC université Paris 06, UMR_S 938, CDR Saint-Antoine, 75005 Paris, France; Unité médicale de transplantation hépatique, UPMC Paris 6, hôpital Pitié-Salpêtrière, AP-HP, boulevard de l'Hôpital, 75013 Paris, France.

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 CD127) 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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http://dx.doi.org/10.1016/j.clinre.2017.10.001DOI Listing
June 2018
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