巨噬细胞在混合嵌合体诱导异种免疫耐受中作用的实验研究  

An experimental study of macrophages on heterogeneous immunotolerance iduced by mixed xenogeneic chimera

作　　者：朱勇[1] 施舜缤[1] 沈振亚[2] 

机构地区：[1]南通大学附属吴江医院胸外科,江苏吴江215200 [2]苏州大学附属第一医院心血管外科,江苏苏州215000

出　　处：《中国医药科学》2013年第18期22-25,31,共5页China Medicine And Pharmacy

摘　　要：目的研究巨噬细胞在建立非协调性异种混合嵌合体中的作用及混合嵌合体的形成对受体的免疫功能影响,探讨异种免疫耐受的机制。方法将非清髓性的预处理SD大鼠(受体)30只随机分成3组,A组(仅输注豚鼠BMC);B组(豚鼠BMC移植组+空脂质体移植组);C组(豚鼠BMC移植组+包裹clodronate脂质体移植组)。观察指标:大鼠肝脾CD68、嵌合体嵌合率、大鼠外周血CD3+T细胞、CD4+T细胞和CD8+T检测、单向混合淋巴细胞反应。结果注射包裹clodronate脂质体后24h受体大鼠肝脾(红髓及边缘带)中巨噬细胞消失,21d后与正常对照相比无差异。BMC移植后24h内各时间点,C组大鼠外周血中豚鼠细胞比例均高于A、B组;24h时大鼠脾、骨髓中豚鼠细胞比例,C组亦明显高于A、B两组;比较21d及35d嵌合水平,C组明显高于A、B两组。21d时CD3+、CD4+和CD8+T细胞比例均下降,各组CD4/CD8比值与对照组相比无差异。MLR显示耐受大鼠的免疫应答反应性降低,C组较其他组比最低。结论增加了供体BMC在受体体内的存活,从而提高嵌合水平,获得了更高水平的免疫抑制。Objective To investigate the effect of macrophages in mixed xenogeneic chimera and explore the mechanisms of immunotolerance in xenotransplantation induced by mixed xenogeneic chimera. Methods Recipient SD rats were divided randomly into three groups. Group A was infused guinea pig bone marrow cells （BMC） only; Group B was injected with blank liposomes; Group C was treated with clodronate-encapsulated liposomes. The percentages of infused labeled guinea pig bone marrow cells in the rat BM and spleen were analyzed by flow cytometry.The level of guinea pig bone marrow cells chimerism in the peripheral blood lymphocyte of recipient rats was detected on 21 day and 35 day by flow cytometry. To explore tolerance mechanisms by performing mixed lymphocyte reaction （MLR）. The flow cytometry was used to check the changes of subgroup of lymphocytes. Results Clodronate-encapsulated liposomes treatment resulted in complete depletion of both liver Kupffer cells and splenic macrophages （red pulp and marginal macrophages）. Macrophages depletion increase the percentages of infused labeled guinea pig bone marrow ceils in the rat blood samples, BM and spleen. Macrophages depletion also improved guinea pig chimerism in rat. MLR in macrophages depletion group was siginificantly decreased comparared with other groups. The lymphocyte＇s subset CD3＋,CD4＋ and CD8＋ count, showed a significant decrease after treatment, but the ratios of CD4/CD8 was indiscriminating among every group. Conclusion Depletion of macrophages with clodronate-encapsulated hposomes can improve guinea pig chimerism in sublethally irradiated rats. Mixed xenogeneic chimera can induce T cells immune suppression.

关 键 词：巨噬细胞 嵌合体 免疫耐受 骨髓移植 

分 类 号：R392.4[医药卫生—免疫学]