PMID- 29175009
OWN - NLM
STAT- MEDLINE
DCOM- 20190603
LR  - 20211204
IS  - 2210-741X (Electronic)
IS  - 2210-7401 (Linking)
VI  - 42
IP  - 3
DP  - 2018 Jun
TI  - Treatment with mTOR inhibitors after liver transplantation enables a sustained 
      increase in regulatory T-cells while preserving their suppressive capacity.
PG  - 237-244
LID - S2210-7401(17)30218-8 [pii]
LID - 10.1016/j.clinre.2017.10.001 [doi]
AB  - 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(low)) 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.
CI  - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved.
FAU - Ghazal, Khaldoun
AU  - Ghazal K
AD  - Sorbonne universites, UPMC universite Paris 06, UMR_S 938, CDR Saint-Antoine, 
      75005 Paris, France; Laboratoire de biochimie, hopital Bicetre, AP-HP, 94275 Le 
      Kremlin-Bicetre cedex, France. Electronic address: khaldoun.ghazal@aphp.fr.
FAU - Stenard, Fabien
AU  - Stenard F
AD  - Sorbonne universites, UPMC universite Paris 06, UMR_S 938, CDR Saint-Antoine, 
      75005 Paris, France.
FAU - Dahlqvist, Geraldine
AU  - Dahlqvist G
AD  - Sorbonne universites, UPMC universite Paris 06, UMR_S 938, CDR Saint-Antoine, 
      75005 Paris, France; Cliniques universitaires Saint-Luc, 1200 Bruxelles, Belgium.
FAU - Barjon, Clement
AU  - Barjon C
AD  - Sorbonne universites, UPMC universite Paris 06, UMR_S 938, CDR Saint-Antoine, 
      75005 Paris, France.
FAU - Aoudjehane, Lynda
AU  - Aoudjehane L
AD  - Sorbonne universites, UPMC universite Paris 06, UMR_S 938, CDR Saint-Antoine, 
      75005 Paris, France.
FAU - Scatton, Olivier
AU  - Scatton O
AD  - Service de chirurgie et de transplantation hepatique, UPMC Paris 6, hopital 
      Pitie-Salpetriere, AP-HP, boulevard de l'Hopital, 75013 Paris, France.
FAU - Conti, Filomena
AU  - Conti F
AD  - Sorbonne universites, UPMC universite Paris 06, UMR_S 938, CDR Saint-Antoine, 
      75005 Paris, France; Unite medicale de transplantation hepatique, UPMC Paris 6, 
      hopital Pitie-Salpetriere, AP-HP, boulevard de l'Hopital, 75013 Paris, France.
LA  - eng
PT  - Journal Article
DEP - 20171123
PL  - France
TA  - Clin Res Hepatol Gastroenterol
JT  - Clinics and research in hepatology and gastroenterology
JID - 101553659
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Everolimus/*pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Immune Tolerance/drug effects
MH  - Immunosuppressive Agents/*therapeutic use
MH  - *Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - Postoperative Care
MH  - Prospective Studies
MH  - Sirolimus/*pharmacology/*therapeutic use
MH  - T-Lymphocytes, Regulatory/*drug effects/*physiology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Tacrolimus/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Calcineurin inhibitor.
OT  - Liver
OT  - Regulatory T-cells
OT  - Transplantation
OT  - mTOR inhibitor
EDAT- 2017/11/28 06:00
MHDA- 2019/06/04 06:00
CRDT- 2017/11/28 06:00
PHST- 2017/05/03 00:00 [received]
PHST- 2017/09/26 00:00 [revised]
PHST- 2017/10/02 00:00 [accepted]
PHST- 2017/11/28 06:00 [pubmed]
PHST- 2019/06/04 06:00 [medline]
PHST- 2017/11/28 06:00 [entrez]
AID - S2210-7401(17)30218-8 [pii]
AID - 10.1016/j.clinre.2017.10.001 [doi]
PST - ppublish
SO  - Clin Res Hepatol Gastroenterol. 2018 Jun;42(3):237-244. doi: 
      10.1016/j.clinre.2017.10.001. Epub 2017 Nov 23.