Mechanism of Immune Hyporesponsiveness Induced by Recipientderived Immature Dendritic Cells in Liver Transplantation Rat

• Published in: 中国医学科学杂志：英文版 no. 1; pp. 28 - 35
• Main Author: Li Li Sheng-ning Zhang Jiang-hua Ran Jing Liu Zhu Li Lai-bang Li
• Format: Journal Article
• Language: English
• Published: 2011
• Subjects: MDCS; Wistar大鼠; 免疫组织化学染色; 反应机制; 成熟; 树突状细胞; 肝移植; 诱导免疫
• ISSN: 1001-9294

Objective To investigate the mechanism of immune hyporesponsiveness induced by donor-antigen- unloaded recipient-derived immature dendritic cell （imDC） of liver grafts in rats. Methods Forty Sprague-Dawley rats （donor） and forty male Wistar rats （recipient） were randomly divided into 4 groups： control, cyclosporine A （CsA）, mature DC （mDC）, and imDC groups respectively, with 10 donor rats and 10 recipient rats in each group. Recipient rats in CsA group were treated with 10 mg-kg-~＇d-I CsA starting day 2 after the transplantation. Recipients in the mDC or imDC groups were given Wistar rat derived mDCs （1 × 10^6/rat） or imDCs （1 × 10^6/rat） via dorsal vein of the penis respectively 1 day before the transplantation. In each group, 5 recipients were kept for determination of survival time and the other 5 rats were executed at day 10 after transplantation. Blood samples were collected for the measurement of serum alanine aminotransferase （ALT）, total bilirubin （TBIL）, interleukin 2 （IL-2）, interferon gamma （IFN-γ）, IL-4, and IL-10 levels. Liver tissue was harvested for HE staining and acute rejection evaluation. Expression levels of Fas-L/Fas in the grafts were detected by immunohistochemical staining; andWestern blot was used to detect the expression level of Scurfm. Results The survival time of CsA and imDC groups was significantly longer than that of control and mDC groups （all P〈0.05）. The levels of serum ALT and TBIL in the control group （2072.20±217.93 IU/L and 147.42±22.02pmol/L） and mDC group （2117.00±285.13 IU/L and 141.58±20.82 pmol/L） were significantly higher than those in the CsA group （59.68±13.48 IU/L and 15.40±2.13 pmol/L） or imDC group （50.80±9.63 IU/L and 14.44±3.49 pmol/L） （all P〈0.05）. In the CsA and imDC groups, the levels of IL-2 （22.52±3.75 pg/mL and 22.12±3.90 pg/mL） and IFN-γ （309.20±25.19 pg/mL and 321.00±21.64 pg/mL） were significantly lower, but the levels of IL-4 （297.60±25.07 pg/mL and 277.00±22.47 pg/mL） and IL-10 （1226.00±140.49 pg/mL and 1423.00±106.39 pg/mL） were higher than those of the control （IL-2：147.78±12.80 pg/mL, IFN-γ： 1758.60±106.22 pg/mL, IL-4：17.40±4.77pg/mL, IL-10： 81.00＋ 9.47 pg/mL） and mDC groups （IL-2：142.34±9.29 pg/mL, IFN-7：1835.00±82.63 pg/mL, IL-4： 15.60＋ 3.96 μg/mL, IL-10： 68.80± 11.23 pg/mL） （all P〈0.01）. The expression level of Scurfin protein on CD4＋CD25 ＋ T cells of the imDC group （1.34±0.29） was significantly higher than that in the control （0.72±0.13）, CsA （0.37±0.11）, and mDC groups （0.78±0.17） （all P〈0.05）.