Rapaport F T, Bachvaroff R J, Watanabe K, Hirasawa H, Mollen N, Ferrebee J W, Amos D B, Cannon F D, Blumenstock D A
J Clin Invest. 1978 Mar;61(3):790-800. doi: 10.1172/JCI108993.
Exposure to supralethal total body irradiation and transplantation of bone marrow from a DLA- and pedigree-identical donor have regularly produced successful engraftment and the establishment of stable long-term chimerism in beagles of the Cooperstown colony. Bone marrow allografts performed in pairs of dogs bearing identical DLA haplotypes derived from different pedigree origins (i.e., different classes of the same haplotype) yielded two different results. Depending upon the particular haplotype pedigree combination used, such transplants either led to long-term chimerism or to failures of engraftment, secondary disease, and death of the recipients (i.e., pedigree-incompatible combinations). Radiation chimeras given bone marrow from a DLA-and pedigree-identical donor were challenged within 8-12 h after marrow transplantation with a renal allograft obtained from another DLA- and pedigree-identical donor. The recipients have remained unresponsive to such renal allografts and have survived indefinitely with normal renal function. In contrast, renal allografts obtained from donors bearing the same DLA haplotypes derived from pedigree-incompatible sources were rejected within 25-50 days after transplantation. The long-term surviving recipients have also been unresponsive to skin allografts obtained from their donor of marrow and the kidney donor. Skin grafts obtained from other DLA- and pedigree-identical dogs were rejected within 13-41 days, and grafts from DLA-incompatible donors survived for 10-25 days. These results highlight the potential importance of genetically controlled histocompatibility determinants other than DLA in conditioning allograft reactivity. The determinants uncovered in the present study appear to be linked to the DLA complex, as demonstrated by the ability of the pedigree origins of DLA haplotypes present in individual dogs to serve as an effective marker system for such non-DLA antigen(s). The results also point to the potential usefulness of the early postirradiation period for the induction of allogeneic unresponsiveness in large adult mammals.
对库珀斯敦犬群的比格犬进行超致死剂量的全身照射，并移植来自DLA和谱系相同供体的骨髓，通常能成功实现植入，并在受体中建立稳定的长期嵌合体。在具有相同DLA单倍型但来自不同谱系来源（即同一单倍型的不同类别）的犬对之间进行骨髓同种异体移植，产生了两种不同的结果。根据所使用的特定单倍型谱系组合，此类移植要么导致长期嵌合体，要么导致植入失败、继发疾病以及受体死亡（即谱系不相容组合）。接受来自DLA和谱系相同供体骨髓的辐射嵌合体，在骨髓移植后8 - 12小时内，接受来自另一个DLA和谱系相同供体的肾移植。受体对这种肾移植一直没有反应，并以正常肾功能无限期存活。相比之下，来自谱系不相容来源、具有相同DLA单倍型供体的肾移植在移植后25 - 50天内被排斥。长期存活的受体对来自其骨髓供体和肾供体的皮肤移植也没有反应。来自其他DLA和谱系相同犬的皮肤移植在13 - 41天内被排斥，而来自DLA不相容供体的移植存活10 - 25天。这些结果突出了除DLA之外的基因控制的组织相容性决定因素在调节同种异体移植反应性方面的潜在重要性。本研究中发现的决定因素似乎与DLA复合体相关，这一点通过个体犬中存在的DLA单倍型的谱系来源能够作为此类非DLA抗原的有效标记系统得以证明。结果还表明，照射后早期对于在大型成年哺乳动物中诱导同种异体无反应性具有潜在的有用性。
