Variation of T cell subset during acute rejection after liver transplantation in rhesus monkeys

doi:10.3969/j.issn.2095-4344.2014.49.014

Abstract

Abstract:

BACKGROUND: Looking for the early diagnosis of acute rejection indicators after liver transplantation can assess the risk after liver transplantation quickly and effectively, and T lymphocytes play the significant role in acute rejection.

OBJECTIVE: To observe the relationship between acute rejection and variation of expression of T cell subset in blood after liver transplantation in rhesus monkey.

METHODS: The sixteen liver transplant models in rhesus monkey which were constructed successfully by the method of “double-cuff and one support tube” were divided into two groups randomly: experiment group (no treated by immunosuppressant in perioperative period) and control group (treated by immunosuppressant in perioperative period). Then the blood specimen and liver tissue respectively were collected at 6, 12, 24 and 72 hours after operation. The levels of alanine transferase, aspartate aminotransferase, and total bilirubin were detected with the fully automatic biochemical analyser. The levels of CD4⁺/CD8⁺were tested by flow cytometry. The liver tissue in rhesus monkey after liver transplantation was detected by hematoxylin-eosin staining. The degree of acute rejection was evaluated by Banff Score System.

RESULTS AND CONCLUSION: Acute rejection appeared in the experiment group at 12, 24, and 72 hours after liver transplantation. Levels of alanine transferase, aspartate aminotransferase, and total bilirubin were significantly higher in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). The expression of CD4⁺/CD8⁺of the experiment group and control group began to rise at 6 hours after surgery, but the experiment group increased the most obvious. CD4⁺/CD8⁺ expression was significantly greater in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). Morphological pathology was severer, and Banff score was higher in the experiment group than in the control group at 72 hours (P < 0.05). These data suggested that the variation of expression of CD4⁺/CD8⁺was earlier than the change of liver tissue pathology and the change of liver function in the early acute rejection after liver transplantation. The rise of level of CD4⁺/CD8⁺ after liver transplantation indicated the increase of cellular immunity in body, which had an important role in the early diagnosis of acute rejection after liver transplantation.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: liver transplantation, macaca mulatta, T-lymphocyte subsets, graft rejection, acute rejection

CLC Number:

R318

Ran Jiang-hua, Liu Jing, Zhang Xi-bing, Zhang Sheng-ning, Wu Shu-yuan, Li Lai-bang, Li Wang, Li Li. Variation of T cell subset during acute rejection after liver transplantation in rhesus monkeys[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(49): 7948-7954.

Figures/Tables 2

Variation of T-lymphocyte subsets In the experiment group without treatment of immunosuppressant, the amounts of CD4+ and CD8+ cells were significantly more than that of control group on the scatter diagram (Figure 1). Regarding the amount of CD4+ and CD8+ cells and the ratio of CD4+/CD8+, there was no significant differences between two groups (P > 0.05) at 6 and 12 hours, but the significant differences were found at 24 and 72 hours (P < 0.05). With the extension of time, the variation trend of CD4+ T cell amount in peripheral blood of experiment group and control group since 6 hours to 72 hours after operation was as follows: CD4+ T cell amount in peripheral blood of experiment group and control group increased with the extension of time; the increasing extent of experiment group was far greater than that of control group; CD8+ T cells amount in peripheral blood of experiment group and control group presented a decreasing trend with the extension of time, the decreasing extent of experiment group was significantly superior to that of control group (Table 1). Variation of biochemical indices of liver damage Comparison of serum alanine transaminase, aspartate aminotransferase and total bilirubin of rhesus monkeys in two groups after liver transplantation: alanine transaminase, aspartate aminotransferase and total bilirubin of experiment group were significantly higher than that of control group at 24 and 72 hours after operation (P < 0.05). The animals in experiment group did not take anti-rejection drugs or hormone after operation, so the damage of hepatic cells caused by the attack of inflammatory cells was more severe than that of control group. Alanine transaminase, aspartate aminotransferase and total bilirubin of two groups presented increasing trend with the extension of time. These three detection indices of two groups were close at 6 and 12 hours after operation, and the differences between two groups had no statistical significance (P > 0.05). Hepatic function presented increasing trend with the extension of time after liver transplantation, the differences of the interior-group in two groups had statistical significance (P > 0.05). Furthermore, the variation of experiment group was greater than of control group, especially from 24 to 72 hours after operation (Table 2). Histopathology of rhesus monkey hepatic tissue after liver transplantation Hepatic tissue of experiment group and control group was basically normal at 6 hours after operation, and no rejection feature was found under microscope (Figure 5, A1 and B1). At the end of 12 hours after operation, hematoxylin-eosin staining indicated the hepatic tissue of experiment group had a mild rejection, Banff score was I-II; the rejection grade of control group was undefined, Banff score was 0-I (Figure 2, A2 and B2). At the end of 24 hours after operation, hematoxylin-eosin staining indicated the hepatic tissue of experiment group had a mediate rejection, Banff score was II-III; control group met the diagnostic criteria of mild acute rejection, Banff score was 0-I (Figure 2, A3 and B3). At the end of 72 hours after operation, hematoxylin-eosin staining indicated the hepatic tissue of experiment group had a severe rejection and Banff score was III; control group presented the mild rejection, and Banff score was 0-I; rejection of the experimental group was severer than in the control group. Significant difference in Banff score was detected between the two groups (P < 0.05) (Figure 5, A4 and B4). Complications All receptors were noted, venous thrombosis and biliary complications. No severe complications of abdominal abscess. Two receptors were visible in hepatic artery thrombosis patients, but not directly killing receptors. "

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