Mixed hematopoietic chimerism induces donor-specific tolerance for lung allografts in rodents.
Mixed hematopoietic chimerism induces donor-specific tolerance for lung allografts in rodents.
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DOI：
10.1164/ajrccm.159.1.9712041
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发表时间：
1999
影响因子：
24.7
通讯作者：
Si.M Pham;Surindra N. Mitruka;W. Youm;Sen Li;N. Kawaharada;S. Yousem;Y. Colson;S. Ildstad
中科院分区：
文献类型：
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作者：
Si.M Pham;Surindra N. Mitruka;W. Youm;Sen Li;N. Kawaharada;S. Yousem;Y. Colson;S. Ildstad
混合造血嵌合是来自两种基因不同动物的骨髓造血干细胞共存的一种状态。我们研究了将宿主和供体骨髓移植到受致命辐射的大鼠体内产生的混合造血嵌合现象是否会赋予供体对同种异体肺移植物的特异性耐受性。受体大鼠（Fisher 或 Wistar Furth [WF]）接受辐射（1,100 cGy），并用 T 细胞耗尽的同基因骨髓和同种异体骨髓的混合物进行重建。骨髓重建后4周，通过外周血中存在供体和宿主来源的细胞来记录混合嵌合体，混合嵌合体接受供体特异性和第三方同种异体肺移植物的原位左肺移植。肺移植后未给予免疫抑制剂。所有供体特异性肺同种异体移植物均被混合嵌合体接受（n = 40），而所有第三方移植物（n = 7）在10天内被排斥，这一时间过程与移植到首次接受者的移植物（n = 14）相似。由于供体骨髓未能移植而未出现混合嵌合的放射对照受者 (n = 7)，也在 10 天内排斥供体特异性移植物。我们得出的结论是，混合造血嵌合诱导供体特异性移植对肺同种异体移植物的耐受性。
Mixed hematopoietic chimerism is a state in which bone marrow hematopoietic stem cells from two genetically different animals coexist. We investigated whether mixed hematopoietic chimerism, resulting from the transplantation of host and donor bone marrow into a lethally irradiated rat, would confer donor-specific tolerance to lung allografts. Recipient rats (Fisher or or Wistar Furth [WF]) were irradiated (1,100 cGy) and reconstituted with a mixture of T-cell-depleted syngeneic plus allogeneic bone marrow. After mixed chimerism was documented by the presence of donor- and host-derived cells in the peripheral blood 4 wk after bone marrow reconstitution, mixed chimeras underwent orthotopic left lung transplantation with donor-specific and third-party lung allografts. No immunosuppressive agents were administered after lung transplantation. All donor-specific lung allografts were accepted by mixed chimeras (n = 40), while all third-party grafts (n = 7) were rejected within 10 d, a time course similar to that for grafts transplanted into naive recipients (n = 14). Radiation control recipients (n = 7) who did not develop mixed chimerism because the donor bone marrow had failed to engraft, also rejected donor-specific grafts within 10 d. We conclude that mixed hematopoietic chimerism induces donor-specific transplantation tolerance to lung allografts.