Granger Darla K, Briedenbach Warren C, Pidwell Diane J, Jones Jon W, Baxter-Lowe Lee Ann, Kaufman Christina L
Department of Surgery, University of Louisville, Louisville, KY, USA.
Transplantation. 2002 Dec 15;74(11):1624-30. doi: 10.1097/00007890-200212150-00022.
Composite tissue allografts offer great potential in reconstructive surgery. However, the risks of immunosuppression and graft-versus-host disease (GVHD) after transplantation of vascularized bone in these grafts are significant. Transplantation of vascularized bone also may confer donor hematopoietic chimerism and, potentially, tolerance. We have followed two hand transplant recipients for more than 1 year to determine the level of chimerism and possible donor-specific tolerance, in addition to possible GVHD.
We performed kinetic studies on peripheral blood of two subjects after hand transplantation that included portions of the radius and ulna. We evaluated donor-specific reactivity, chimerism, and antibody production.
Donor-specific tolerance did not develop clinically or in mixed lymphocyte reaction. The first subject recovered an excellent in vitro response to phytohemagglutinin, donor and third-party alloantigen, and by month 4 and at month 12 also recovered the ability to respond to Epstein-Barr virus. The second subject also demonstrated good in vitro proliferative responses, which were attenuated by immunosuppression. No phenotypic changes in mature hematopoietic lineages were detected by four-color flow cytometry other than those expected in response to immunosuppression. Donor chimerism was not detectable using four-color flow cytometry. Microchimerism (approximately 1:75,000 cells) was observed at the level of detection in some of the early posttransplantation specimens and was undetectable thereafter.
In this particular transplantation and immunosuppressive regimen, the composite tissue allograft with vascularized bone marrow did not provide the immunologic benefit of tolerance induction nor cause GVHD.
复合组织同种异体移植在重建外科手术中具有巨大潜力。然而，这些移植组织中血管化骨移植术后免疫抑制和移植物抗宿主病（GVHD）的风险很大。血管化骨移植还可能导致供体造血嵌合体，并有可能诱导免疫耐受。除了可能发生的GVHD外，我们对两名手部移植受者进行了一年多的随访，以确定嵌合体水平和可能的供体特异性耐受情况。
我们对两名接受包含部分桡骨和尺骨的手部移植患者的外周血进行了动力学研究。我们评估了供体特异性反应性、嵌合体和抗体产生情况。
在临床或混合淋巴细胞反应中均未出现供体特异性耐受。第一名受试者恢复了对植物血凝素、供体和第三方同种异体抗原的良好体外反应，到第4个月和第12个月时，还恢复了对EB病毒的反应能力。第二名受试者也表现出良好的体外增殖反应，但被免疫抑制所减弱。除了免疫抑制所预期的变化外，四色流式细胞术未检测到成熟造血谱系的表型变化。使用四色流式细胞术未检测到供体嵌合体。在一些移植后的早期标本中检测到微嵌合体（约1:75,000细胞），此后未检测到。
在这种特定的移植和免疫抑制方案中，带有血管化骨髓的复合组织同种异体移植既未提供诱导耐受的免疫益处，也未引起GVHD。
