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抗T细胞受体αβ单抗和抗CD80单抗联合供体骨髓移植诱导小鼠皮肤移植耐受
  • ISSN号:1671-167X
  • 期刊名称:《北京大学学报:医学版》
  • 时间:0
  • 分类:R392.4[医药卫生—免疫学;医药卫生—基础医学]
  • 作者机构:[1]北京大学基础医学院免疫学系,北京100083
  • 相关基金:国家自然科学基金(39830340)资助
中文摘要:

目的:探讨抗T细胞受体(T cell receptor,TCR)αβ单抗和抗CD80单抗联合供体骨髓细胞输注方法在同种异基因小鼠皮肤移植耐受诱导中的作用。方法:第0天,向C57BL/6小鼠(受体)尾静脉输注2×10^8个BALB/c小鼠(供体)来源的骨髓细胞,同时腹腔注射抗TCRαβ单抗500μg;第2天,向C57BL/6小鼠腹腔注射抗CD80单抗500μg。第6天进行皮肤移植。在不同的时间对C57BL/6小鼠进行迟发型超敏反应测定和混合淋巴细胞反应(mixed lymphocyte reaction,MLR)分析,并进行MLR的白细胞介素-2(interleukin-2,IL-2)逆转实验、过继转移实验和嵌合体检查,探讨耐受形成的机制。结果:接受了抗TCRαβ单抗和抗CD80单抗联合供体骨髓移植的C57BL/6小鼠,供体皮肤移植物平均存活70d;在迟发型超敏反应和t昆合淋巴细胞反应中均表现出显著的低反应性。IL-2逆转实验结果表明克隆不应答可能参与了移植耐受的形成。体内、体外过继转移实验均显示耐受C57BL/6小鼠脾细胞中存在抑制细胞的活性。嵌合体检查结果表明在耐受C57BL/6小鼠的胸腺和脾中均形成了混合嵌合体,嵌合体水平随时间下降。结论:抗TCRαβ单抗和抗CD80单抗联合大剂量供体骨髓细胞输注可以在组织相容性抗原完全不相同的成年小鼠间成功诱导出皮肤移植物的长期耐受。

英文摘要:

Objective: To explore the role of anti-αβ T cell receptor (TCR) and anti-CD80 monoclonal antibodies (mAbs) combined with donor bone marrow cells (BMCs) infusion in the induction of murine skin allografts tolerance. Methods: On day 0.2 × 10^8 BMCs of BALB/c mice were injected into recipient C57BL/6 mice via the tail vein, meanwhile, an intraperitoneal injection of TCRαβ mAb (500μg) was given. On day 2, CD80 mAb was administered intraperitoneally. Skin grafting was performed on day 6. Delayed type hypersensitivity ( DTH), mixed lymphocyte reaction ( MLR), IL-2 reverse assay of MLR, adoptive transfer assay and chimerism detection were performed at different time points and tolerance mechanisms were investigated. Results: The mean survival time (MST) of BALB/c skin allografts in C57BL/6 recipients that were treated by anti-TCRαβ and anti-CD80 mAbs combined with donor BMCs infusion was 70 days. DTH and MLR assay indicated that the tolerant mice displayed significant hyporesponsiveness. The result of IL-2 reverse test showed that clone anergy was probably involved in the formation of tolerance in the tolerant C57BL/6 mice. In vivo and in vitro adoptive transfer assay, suppressive activity in the spleens of tolerant C57BL/6 mice was observed. Chimerism existed in both the thymus and spleen of the tolerant C57BL/6 mice. The chimerism level gradually declined with time. Conclusion: Treatment of anti-TCRαβ and anti-CD80 mAbs combined with donor BMCs infusion can successfully induce a long-term tolerance in BALB/c mice to C57BL/6 skin graft. Multiple mechanisms, including clone anergy, suppressor cells and chimerism are involved in the tolerance.

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期刊信息
  • 《北京大学学报:医学版》
  • 北大核心期刊(2011版)
  • 主管单位:中华人民共和国教育部
  • 主办单位:北京大学
  • 主编:韩启德
  • 地址:北京海淀区学院路38号
  • 邮编:100191
  • 邮箱:
  • 电话:010-82801551
  • 国际标准刊号:ISSN:1671-167X
  • 国内统一刊号:ISSN:11-4691/R
  • 邮发代号:2-489
  • 获奖情况:
  • 1992年全国优秀科技期刊评比三等奖,1996年第二届全国优秀科技期刊评比二等奖,2001年入选中国期刊方阵,被评为“双百”期刊,2007年获得第六届百种中国杰出学术期刊奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),波兰哥白尼索引,荷兰文摘与引文数据库,美国生物医学检索系统,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版)
  • 被引量:16532