Role of CTLA4-Ig and anti-CD40L monoclonal antibody in the immune rejection of pancreas transplantation in rats
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 6
- DOI:
- 10.3760/cma.j.issn.0254-1785.2007.06.002
- Key Word:
- 胰腺移植;免疫耐受;抗CD40L单克隆抗体;大鼠
Abstract： 目的 探讨细胞毒T淋巴细胞相关抗原4免疫球蛋白(CTLA4-Ig)和抗CD40L单克隆抗体对异基因大鼠胰腺移植后急性排斥反应的作用及其相关机制.方法 建立大鼠的胰十二指肠移植模型,供者为F344大鼠,受者为经链尿佐菌素诱导为糖尿病模型的Lewis大鼠,受者移植后分为4组,每组12只.A组:为应用生理盐水对照组;B组:应用CTLA4-Ig 200 μg;C组:应用抗CD40L单克隆抗体200 μg;D组:联合应用CTLA4-Ig和抗CD40L单克隆抗体各200 μg.各组分别于术后第2d腹腔注射相应的药物.术后1、4、7、10 d分别取各组的移植胰腺,进行常规病理检测;采用逆转录聚合酶链(RT-PCR)法检测移植物白细胞介素2(IL-2)、白细胞介素4(IL-4)、白细胞介素10(IL-10)、γ干扰素(IFN-γ)的表达;术后第1、4、7、10 d取受者外周血,采用流式细胞术计数T细胞亚群CD3+、CD4+和CD8+;术后第4 d取移植胰计数CD4+CD25+T细胞.结果 病理检测显示:与A组相比,B、C组排斥反应明显减弱,D组几乎未发生排斥反应;B、C、D组IL-2的表达高峰延迟,且表达水平较A组有不同程度的降低,D组又较B、C组表达水平下降,差异有统计学意义;B、C、D组IFN-γ的表达水平较A组有不同程度的降低,但D组与B、C组的差异不显著;B、C组IL-4的表达水平较A组有不同程度的升高,D组较A、B、C组表达水平下降,差异有统计学意义;B、C组IL-10的表达水平较A组有不同程度的升高,D组与A组差异不显著;B、C、D组CD3+、CD4+和CD8+T细胞数均相对减少,CD4+CD25+T细胞数有不同程度升高,与A组比较,D组的差异最为显著.结论 联合应用CTLA4-Ig和抗CD40L单克隆抗体能更有效地抑制大鼠胰腺移植后排斥反应,其机制可能与Th1/Th2型细胞因子偏移及CD4+CD25+调节性T细胞增多等有关.
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