el Badri N S, Good R A
All Children's Hospital, University of South Florida, St. Petersburg 33701.
Proc Soc Exp Biol Med. 1994 Jan;205(1):67-74. doi: 10.3181/00379727-205-43679.
Bone marrow transplantation (BMT) has been used to induce and maintain immunological tolerance. Such tolerance could facilitate tissue and organ transplantation between the donor and the recipient without need for continuous immune suppression. A protocol employing transplantation of a mixture of T-cell depleted (TCD) syngeneic plus TCD-allogeneic bone marrow cells has been successfully used for induction of transplantation tolerance between mice that differ at components of the major histocompatibility barrier (MHC), or for crossing the xenogenic barrier. We examined the production of specific immunological tolerance using mixed syngeneic plus allogeneic TCD-BMT to cross the entire major plus multiminor histocompatibility barriers. The transplanted mice were repopulated in a stable manner with a mixture of both donor and recipient phenotypes. On histological examination, the mice were reconstituted with hemopoietic and immunocompetent lymphocytes as assayed by their responses to the thymus-dependent cellular antigen, sheep red blood cells (SRBC) in an in vivo plaque-forming cell assay. The transplanted mice were found to be stable chimeras and expressed long lasting tolerance of both donor and recipient cells and yet they were fully reactive to third party cells in mixed lymphocyte culture. These results provide evidence that "supportive" or accessory cells in the syngeneic marrow facilitate maturation of donor marrow cells into fully functioning immunocytes in an allogeneic environment crossing the MHC barrier, which represents the greatest known challenge to allogeneic marrow transplantation in mice. The MHC-mismatched mixed allogeneic transplantation method may improve organ engraftment in human recipients of BMT from a partially mismatched donor or from a cadaver donor, and may significantly improve graft acceptance from a fully matched sibling donor.
骨髓移植（BMT）已被用于诱导和维持免疫耐受。这种耐受可促进供体和受体之间的组织和器官移植，而无需持续的免疫抑制。一种采用T细胞去除（TCD）同基因加TCD异基因骨髓细胞混合物移植的方案已成功用于诱导主要组织相容性屏障（MHC）成分不同的小鼠之间的移植耐受，或跨越异种屏障。我们使用混合同基因加异基因TCD-BMT来跨越整个主要加多个次要组织相容性屏障，研究了特异性免疫耐受的产生。移植的小鼠以稳定的方式重新填充了供体和受体两种表型的混合物。组织学检查显示，在体内空斑形成细胞试验中，通过小鼠对胸腺依赖性细胞抗原绵羊红细胞（SRBC）的反应检测，小鼠由造血和具有免疫活性的淋巴细胞重建。发现移植的小鼠是稳定的嵌合体，对供体和受体细胞均表现出持久的耐受性，但在混合淋巴细胞培养中对第三方细胞具有完全反应性。这些结果证明，同基因骨髓中的“支持性”或辅助细胞有助于供体骨髓细胞在跨越MHC屏障的异基因环境中成熟为功能完全的免疫细胞，这是小鼠异基因骨髓移植面临的最大已知挑战。MHC不匹配的混合异基因移植方法可能会改善来自部分不匹配供体或尸体供体的BMT人类受体的器官植入，并可能显著提高来自完全匹配同胞供体的移植物接受率。
