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Early reduction of regulatory T cells is associated with acute rejection in liver transplantation under tacrolimus-based immunosuppression with basiliximab induction

 Ji Won Han  ;  Dong Jin Joo  ;  Jong Hoon Kim  ;  Min-Seok Rha  ;  June Young Koh  ;  Hye Jung Park  ;  Jae Geun Lee  ;  Myoung Soo Kim  ;  Soon Il Kim  ;  Eui-Cheol Shin  ;  Jun Yong Park  ;  Su-Hyung Park 
 AMERICAN JOURNAL OF TRANSPLANTATION, Vol.20(8) : 2058-2069, 2020-08 
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immunobiology ; immunosuppressant - calcineurin inhibitor (CNI) ; immunosuppression/immune modulation ; liver transplantation/hepatology ; lymphocyte biology ; rejection ; acute ; translational research/science
Regulatory T (Treg) cells are important in preventing acute rejection (AR) in solid organ transplantation, but the clinical relevance of the different kinetics early after liver transplantation (LT) in acute rejectors and non-rejectors is unclear. We analyzed peripheral blood samples of 128 LT recipients receiving basiliximab induction plus tacrolimus immunosuppression. Samples were obtained at pretransplant, D7, and D30 after LT. Frequency and phenotype of Tregs were analyzed by flow cytometry. The predictive value of Treg frequency at D7 was assessed for suspected acute rejection (SAR) and was validated for biopsy-proven AR (BPAR). We found that the frequencies of total and activated Tregs at D7 were significantly lower in recipients with SAR and BPAR. Treg was more reduced in BPARs by in vitro tacrolimus treatment in the presence of basiliximab. Moreover, an early reduction of Treg frequency in rejectors was associated with a greater increase in Treg apoptosis and further attenuated IL-2 signaling. D7 Treg frequency was an independent risk factor for SAR, which was also validated for BPAR. In conclusion, first-week peripheral blood Treg frequency correlates with AR after LT under tacrolimus-based immunosuppression, which needs to be proven in larger, geographically and clinically diverse populations.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Soon Il(김순일) ORCID logo https://orcid.org/0000-0002-0783-7538
Kim, Jong Hoon(김종훈) ORCID logo https://orcid.org/0000-0002-3385-8180
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Park, Hye Jung(박혜정) ORCID logo https://orcid.org/0000-0002-1862-1003
Lee, Jae Geun(이재근) ORCID logo https://orcid.org/0000-0002-6722-0257
Joo, Dong Jin(주동진) ORCID logo https://orcid.org/0000-0001-8405-1531
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