抗淋巴细胞血清联合脾细胞促进异基因骨髓细胞形成嵌合体诱导免疫耐受(1)

http://www.100md.com 2008年2月1日 《现代医药卫生》 2008年第3期

     【摘要】目的：探讨抗淋巴细胞血清(ALS)联合异基因脾细胞(SC)在促进异基因骨髓细胞移植诱导小鼠皮肤移植免疫耐受中的作用。方法：第-5~-3天，C57BL/6(H-2b)受体小鼠每天腹腔注入0.5 ml抗淋巴细胞血清(ALS)，共3天。第0天，C57BL/6受体小鼠通过尾静脉输注均源自BALB/c(H-2d)的1×108脾细胞(SC)及2×107骨髓细胞(BMC)。第二天，受体鼠腹腔注入200 mg/kg的环磷酰胺(CP)。第六天进行从BALB/c到C57BL/6的尾-尾皮肤移植。每天观察移植皮片存活情况，共观察100天。并于骨髓细胞移植后30天、50天及70天对受体小鼠外周血进行嵌合体检查。结果：抗淋巴细胞血清和(或)异基因脾细胞的输注能促进异基因BMC的植入，并能延长移植皮片的存活时间。在30、50天及70天，SC+BMC+CP、ALS+BMC+CP及ALS+SC+BMC+CP移植组受体小鼠体内能检测到供体骨髓源性细胞，ALS+SC+BMC+CP移植组的嵌合率较高，随着时间推移，嵌合率下降，而且移植皮片存活时间与嵌合率具一定相关性。结论：抗淋巴细胞血清(ALS)联合异基因脾细胞能协助异基因BMC植入，形成嵌合体，促进免疫耐受的诱导，使移植皮片存活时间延长。

    【关键词】抗淋巴细胞血清；脾细胞；骨髓细胞；嵌合体；免疫耐受；皮肤移植

    文章编号：1009-5519(2008)03-0319-02 中图分类号：R392 文献标识码：A

    Antilymphocyte serum plus allogeneic spleen cells infusion facilitating allogeneic bone marrow cells

    engraftment and promoting the induction of murine skin allograft tolerance

    ZHANG Wen-yuan，YANG Ya-dong，FANG Guo-jian，et al.

    (Institute of Biological Engeneering，Zhejiang Academy of Medical Science，Hangzhou 310013，China)

    【Abstract】Objective：To explore the effect of antilymphocyte serum plus allogeneic spleen cells infusion in facilitating allogeneic bone marrow cells engraftment and promoting the induction of murine skin allograft tolerance.Methods：C57BL/6(H-2b)recipient mice were primed intraperitoneally (i.p.) with 0.5ml antilymphocyte serum (ALS)/day for three days on day -5~-3，then were injected intravenously (i.v.) with 1×108 spleen cells (SC) and 2×107 bone marrow cells (BMC) from BALB/c(H-2d)mice on day 0. The recipient mice were treated i.p. with 200mg/kg of cyclophosphamide on day 2. Tail-to-tail skin grafting from BALB/c to C57BL/6 was carried out on day 6. Survival time of the skin allografts was observed every day， and chimerism level was investigated on day 30，day 50 and day 70. Results：It was found that administration of antilymphocyte serum plus allogeneic spleen cells combined with allogeneic BMC could result in prolonged skin allograft survival. The survival time of BALB/c skin allografts in C57BL/6 recipients that were treated by antilymphocyte serum plus allogeneic spleen cells combined with high dose of allogeneic BMC infusion was significant ro modest longer than that of other groups. Chimerism could be obtained on day 30，day 50 and day 70 in groups of allogeneic BMC infusion，and chimerism level of antilymphocyte serum and allogeneic spleen cells plus BMC infusion was higher than that of another groups. In the recipient mice，the survival time of skin allografts seemed to be positively correlated with chimerism level. Conclusion：Antilymphocyte serum plus allogeneic spleen cells could facilitate allogeneic BMC engraftment and promote inducion of immune tolerance in BALB/c to C57BL/6 skin allografts.

    【Key words】Antilymphocyte serum；Spleen cell；Bone marrow cell；Chimerism；Immune tolerance；Skin transplantation

    器官移植是终末期器官功能衰竭的有效治疗手段，近年来出现许多新型免疫抑制剂，使移植排斥反应大大减弱，延长了移植物的存活时间及存活率。但长期服药带来的不良作用以及慢性排斥无法得到有效解决，对受体进行强烈的预处理，如化学毒性药物处理、照射等，在临床上难以接受，最佳方法是诱导一种持久稳定无需药物的免疫耐受来解决这一难题。通过骨髓移植形成嵌合体是诱导免疫耐受的有效手段，通过建立嵌合体诱导免疫耐受是目前解决器官移植的重要课题。抗淋巴细胞血清(ALS)是一种很强的免疫抑制剂，可使异基因小鼠皮肤移植时间延长，ALS联合异基因脾细胞输注能否协助异基因骨髓细胞(BMC)植入，形成嵌合体，并建立特异性免疫耐受。我们寻求较温和非照射，而又能诱导稳定嵌合体的方法，利用ALS联合异基因脾细胞协同异基因骨髓移植诱导异基因小鼠皮肤移植的免疫耐受状态，并对诱导耐受的机制进行了初步的探讨。(张文元　杨亚冬　房国坚　陈　勇)

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