Glass B, Uharek L, Gaska T, Gassmann W, Löffler H, Müller-Ruchholtz W
Department of Internal Medicine II, University of Kiel, Germany.
Bone Marrow Transplant. 1993;12 Suppl 3:S41-7.
Graft rejection has hampered the use of T cell depletion (TCD) in allogeneic bone marrow transplantation. A model of host-versus-graft (HVGR) and graft-versus-host reaction (GVHR) as two inversely related processes has been proposed. We investigated graft rejection rates in graft-versus-host-reactive and graft-versus-host-nonreactive situations in a rat and a mouse model. Model 1: LEW rats were pretreated with a fixed myeloablative dose of busulfan and increasing doses of the immunosuppressive cyclophosphamide. The animals received different doses of semiallogeneic GvH-nonreactive BM cells. Graft rejection rates were dependent on the bone marrow cell number transplanted and on the pretransplant immunosuppression. Graft rejection rates following transplantation of GvH-reactive CAP marrow and genetically GvH-nonreactive (CAP x LEW)F1 marrow were the same. In conclusion, there was no advantage with respect to engraftment for the GvH-reactive marrow. Model 2: In irradiated Balb/c mice, graft rejection rates following T cell-depleted and unmanipulated transplantation of GvH-reactive or GvH-nonreactive bone marrow grafts were identical. All experiments were done with graded numbers of BM cells and revealed a strong impact of the BM cell dose on engraftment. In our experiments the cell loss during the ex-vivo manipulation was approximately 50% and, in contrast to the clinical situation, we readjusted to the intended number after TCD. Our experiments demonstrate that neither GvHR nor T cells but the BM cell dose has a strong impact on engraftment of allogeneic bone marrow.
移植物排斥反应阻碍了T细胞清除（TCD）在异基因骨髓移植中的应用。有人提出了宿主抗移植物反应（HVGR）和移植物抗宿主反应（GVHR）这两个相互反向关联过程的模型。我们在大鼠和小鼠模型中研究了移植物抗宿主反应性和非反应性情况下的移植物排斥率。模型1：用固定剂量的白消安进行清髓预处理，并给予递增剂量的免疫抑制药物环磷酰胺处理LEW大鼠。这些动物接受不同剂量的半同种异体GVH非反应性骨髓细胞。移植物排斥率取决于移植的骨髓细胞数量和移植前的免疫抑制情况。移植GVH反应性CAP骨髓和基因上GVH非反应性（CAP×LEW）F1骨髓后的移植物排斥率相同。总之，GVH反应性骨髓在植入方面没有优势。模型2：在经照射的Balb/c小鼠中，T细胞清除和未处理的GVH反应性或GVH非反应性骨髓移植物移植后的移植物排斥率相同。所有实验均使用不同数量级的骨髓细胞进行，结果显示骨髓细胞剂量对植入有很大影响。在我们的实验中，体外操作过程中的细胞损失约为50%，并且与临床情况不同的是，TCD后我们将细胞数量重新调整至预期数量。我们的实验表明，对异基因骨髓植入有很大影响的既不是GVHR也不是T细胞，而是骨髓细胞剂量。
