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2×108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(m ixed lymphocyte reaction,MLR)分析,并进行MLR的白细胞介素-2(interleuk in-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70 d;在迟发型超敏反应和混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。
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.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2006年第4期365-369,共5页
Journal of Peking University:Health Sciences
基金
国家自然科学基金(39830340)资助~~
关键词
抗体
单克隆
嵌合体
骨髓细胞
皮肤移植
移植耐受
Antibodies, monoclonal
Chimera
Bone marrow cells
Skin transplantation
Transplantation tolerance
