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在不对受体去髓处理的情况下,用重组腺病毒AdCTLA4-FasL结合供者骨髓移植诱导混合嵌合体和同种皮肤移植耐受,结果显示,获得了持久宏嵌合体(macrochimerism)(140d时,供体细胞>20%).同时,这种嵌合体促进了稳定的供体特异性耐受,BALB/c小鼠的皮肤移植物在B6受体小鼠中长期存活(平均存活时间(themeansurvivaltime,MST)大于200d),而来源于ICR小鼠的第三者皮肤移植物被该嵌合体小鼠正常排斥.用该方法处理的B6小鼠在接受皮肤移植14d后,辅助性T淋巴细胞前体(HTLp)和细胞毒T淋巴细胞前体(CTLp)的频数降低到很低的水平,表明AdCTLA4-FasL能够迅速促进全面的外周耐受,从而有利于供体骨髓细胞植入.接受皮肤移植140d后,供体皮肤仅在形成长期嵌合体的受体小鼠中继续存活,这些小鼠体内供体特异性的HTLp和CTLp的频数减少,提示长期的皮肤移植物耐受与稳定的混合嵌合体有关,中枢性T细胞删除可能是耐受维持的主要机制.
Induced mixed chimerism and allograft tolerance with recombinant adenovirus AdCTLA4-FasL in combination with donor bone marrow transplantation without demyelinating the receptor revealed that macrochimerism (140 d , Donor cells> 20%.) At the same time, this chimera promoted stable donor-specific tolerance, skin grafts from BALB / c mice long-term survival in B6 receptor mice (themeansurvivaltime , MST) greater than 200d), while third-generation skin grafts derived from ICR mice were normally rejected by the chimeric mice.The B6 mice treated with this method were exposed to pre-T lymphocytes for 14 days (HTLp) and cytotoxic T lymphocyte precursors (CTLp) decreased to a very low level, indicating that AdCTLA4-FasL can quickly promote the overall peripheral tolerance, which is conducive to donor bone marrow cells transplantation. Receiving skin grafts After 140 days donor skin continued to survive only in recipient mice that formed long-term chimeras, and the frequency of donor-specific HTLp and CTLp was reduced in these mice, suggesting long-term skin graft tolerance and stable mixed inlays Associated with central T cell deletion Is the primary mechanism tolerance can be maintained.