小鼠同基因型移植物抗宿主病发生机制及其意义

Immunological Mechanism of Mouse Syngeneic Graft Versus Host Disease Model and Its Significance

目的：初步探讨小鼠同基因型移植物抗宿主病(SGVHD)的发生机制,为研究移植物抗白血病效应奠定基础。方法：用同基因骨髓细胞重建致死剂量X线照射的小鼠,用环孢素A(CsA)腹腔注射诱导治疗21d。停药后每日观察小鼠临床症状,在小鼠出现GYHD样症状时,取肝脏、结肠、耳朵、皮肤和胸腺进行组织学检查,并检测肝脏、结肠组织细胞因子和协同刺激分子的表达。结果：67％(19／28)的模型组小鼠产生GVHD样症状,组织病理检查发现GVHD样小鼠结肠和肝脏有组织坏死和大量炎细胞浸润,而移植对照组均未出现GVHD样症状,组织学未见明显异常。R7-PCR检测发现GVHD样小鼠结肠和肝脏组织中共刺激分子CD137mRNA水平和细胞因子IL-12、IFN-Υ和TNF-α mRNA水平较移植对照组小鼠的水平升高。结论：CsA可诱导同基因型骨髓移植小鼠产生GVHD样症状,Th1类细胞因子参与了SGVHD的发生,为进一步研究$GVHD的抗肿瘤机制建立了技术平台。

Objective： To primarily explore the immunological mechanism of SGVHD and provide a platform for study of graft-versus leukemia. Methods： Lethally irradiated C3H/HeJ mice were reconstructed with syngeneic bone marrow cells and induced with cyclosporine （CsA） for 21d. After cessation of CsA , the clinical symptoms of SGVHD（such as weight loss, diarrhea, hunching, runting） were observed. The histological changes of murine liver, colon, skin, thymus and ear were examined by routine pathological methods. Meanwhile, the expression of cytokines in mice colon and liver were examined by RT-PCR. Results： 67% （ 19/28 ） of mice developed GVHD - like clinical symptom in SGVHD-induced group and their pathological detection of liver and colon showed tissue necrosis and increased lymphocyte infiltration . The levels of costimulatory molecule （ CD137 ） and Th1-type cytokines（ IL-12, IFN-γ, and TNF-α） mRNA were enhanced in liver and colon of SGVHD mice, compared with control mice. Conclusion： The CsA can induce syngeneic BMT recipients of C3H/HeJ mice to develop SGVHD, and costimulatory molecules and Thl type cytokines played an important role in development of SGVHD.