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. 2018 Jun 4;15(9):892-899.
doi: 10.7150/ijms.24042. eCollection 2018.

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
Affiliations

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

Lei Geng et al. Int J Med Sci. .

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; Rejection; Tacrolimus.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
(A-C) The proportion of CD8Ts in a recipient without graft dysfunction (A), a patient with graft dysfunction (B), and a recipient with immunosuppressant withdrawal (C). (D) Summary data showing the proportion of CD8Ts among groups. (E) CD8T proportions in relation to recovery of graft function in recipients with rejection. (F) CD8T proportions in patients with refractory graft dysfunction.
Figure 2
Figure 2
(A) The proportion of CD8Ts in recipients as function of age. (B) The proportion of CD8Ts in patients in >10, 5-10, and 0-5 ng/ml tacrolimus groups. (C, D) Proportion of CD8Ts in patients during the first year after LT (C) and at later time points (D).
Figure 3
Figure 3
(A, B) The number of lymphocytes (A) and absolute value of CD8Ts (B) in graft-dysfunction and normal graft function groups. There were no significant differences between groups. (C, D) Median proportion of CD8+CD28+ T cells (C) and ΔCD8T proportion (D) in the normal function group and graft-dysfunction group.
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