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Int J Med Sci 2018; 15(9):892-899. doi:10.7150/ijms.24042

Research Paper

A high frequency of CD8⁺CD28^- T-suppressor cells contributes to maintaining stable graft function and reducing immunosuppressant dosage after liver transplantation

Lei Geng^1,2,3,*, Jingfeng Liu^1,2,3,*, Junjie Huang^1,2,3, Bingyi Lin^1,2,3, Songfeng Yu^1,2,3, Tian Shen^1,2,3, Zhuoyi Wang^1,2,3, Zhe Yang^1,2,3, Lin Zhou^1,2,3, Shuseng Zheng^1,2,3,✉

1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China
2. Division of Liver Transplantation, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China
3. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
*These authors contribute equally to the study.

Abstract

CD8⁺CD28^-T cells (CD8Ts) exert immunosuppressive effects in various autoimmune diseases. The current study was designed to investigate the role of defects in CD8Ts in liver transplantation (LT). The proportion of CD8Ts in peripheral blood was determined by flow cytometry. The mean proportion of CD8Ts was 23.39% in recipients with stable graft function and 16.64% in those with graft dysfunction following LT compared with 19.86% in the healthy cohort. After receiving enhanced immunosuppressive therapy, patients in the rejection group who achieved recovery of graft function showed an increase in the proportion of CD8Ts (from 17.39% to 25.55%), but those in the group with refractory graft dysfunction showed no significant change (12.49% to 10.30%). Furthermore, in the first year after LT, recipients longer removed in time from the LT date exhibited a higher proportion of CD8Ts. Patients benefited most from tacrolimus concentrations of 5-10 ng/ml in the first year after LT and 0-5 ng/ml thereafter. Moreover, the change in the proportion of CD8Ts (ΔCD8Ts) was significantly higher in recipients with stable graft function than in those with graft dysfunction. These results suggest that a high frequency of CD8Ts prevents rejection and contributes to reduce immunosuppressant dosage and even induces tolerance.

Keywords: CD8⁺CD28^-T cells, Liver transplantation, Tacrolimus, Rejection