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本研究通过非清髓性预处理方案联合髓腔内骨髓移植(IBMBMT)建立异基因小鼠免疫耐受模型,并探讨其诱导耐受的机理。受鼠为雌性C57BL/6(H2b,B6)小鼠,于第0天接受60Coγ线全身照射(TBI),4小时内输注雄性BALB/c(H2d)小鼠来源的骨髓细胞(BMC),2天后腹腔注射环磷酰胺(CTX)。通过皮肤移植、混合淋巴细胞反应(MLR)检测耐受状态,并通过体外过继转移实验、IL2逆转实验等探讨免疫耐受的机制。结果显示,经骨髓移植的B6小鼠对BALB/c小鼠的皮肤移植物平均存活时间(MST)>150天,较对照组明显延长(P<0.01);骨髓移植后第90天,受鼠(黑色)表型开始呈现供鼠(白色)颜色特征。MLR结果证明,B6小鼠获得供体特异性耐受,该耐受可以被IL2逆转且可被过继转移;所有受鼠均未出现GVHD表现。结论:非清髓预处理联合髓腔内骨髓移植可以有效地诱导异基因小鼠免疫耐受,克隆无能、抑制细胞存在及嵌合体产生均参与耐受的形成。
In this study, non-myeloablative preconditioning combined with intramedullary bone marrow transplantation (IBMBMT) to establish allogeneic mice immune tolerance model and explore its mechanism of induction of tolerance. The mice were female C57BL / 6 (H2b, B6) mice receiving 60Co gamma-ray whole body irradiation (TBI) on day 0 and bone marrow cells (BMC) derived from male BALB / c Cyclophosphamide (CTX) was injected intraperitoneally 2 days later. Tolerance status was detected by skin graft and mixed lymphocyte reaction (MLR), and the mechanism of immune tolerance was explored through adoptive transfer in vitro and IL2 reversal test. The results showed that the average survival time (MST) of BALB / c mice> 150 days was significantly longer in B6 mice than in control mice (P <0.01). On the 90th day after bone marrow transplantation, (Black) phenotype began to appear for the mouse (white) color characteristics. MLR results demonstrated that B6 mice acquired donor-specific tolerance that was reversible by IL2 and adoptively transferred; none of the mice developed GVHD performance. CONCLUSION: Non-myeloablative preconditioning combined with intramedullary bone marrow transplantation can effectively induce immune tolerance in allogeneic mice. Incompatibility of clonality, suppression of cell existence and generation of chimeras are all involved in the formation of tolerance.