GRAFT-VERSUS-HOST DISEASE IN ALLOGENEIC BONE MARROW TRANSPLANTATION

移植物抗宿主病(GvHD)的发生依赖于 慢性粒细胞白血病供者骨髓中免疫活性T细胞的存在 宿主同种异体抗原的特异性。激活 在输注后宿主中的这些细胞和所产生的组织 损伤在临床上被认为是移植物抗宿主病。一种方法是 预防GvHD的方法是将这些T细胞从骨髓中移除 接种剂。我们一直致力于去除人类骨髓中的T细胞 骨髓移植中预防移植物抗宿主病的作用 通过使用针对人类的特异性单抗来区分人类 T细胞特有的细胞表面分子与 互补性。已经产生了两种这样的抗体，其中一种是 CD2(绵羊红细胞受体)的特异性和一种 定义了一种新的T细胞决定簇。后一种抗体-- 在非晶态条件下形成一个92kD的分子和一个主要的45kD带 还原条件和还原条件。这些 两种抗体，结合CD7和CD5特异性 抗体，已被用于在人类骨骼中进行研究 骨髓T细胞耗尽。对残留在骨髓中的T细胞进行量化 在这种耗尽之后，发展了一种限制稀释试验。 它检测T细胞的水平是每10-10个骨髓一个T细胞 细胞。一组被冷冻保存的骨髓被一种 单抗和补体的组合，与 通过极限稀释试验评估的耗竭程度， 已经建立并开发了一项临床方案来评估 利用这些骨髓治疗骨髓瘤的可行性研究 侵袭性恶性肿瘤伴骨髓切除联合化疗 和放射治疗。

Graft-versus-host disease (GvHD) is dependent in its generation on the presence of immune competent T cells in the donor marrow with specificity for allogeneic antigens of the host. The activation of these cells in the host after infusion and the resultant tissue injury is clinically recognized as GvHD. One approach to preventing GvHD is the removal of these T cells from the marrow inoculum. We have pursued T cell depletion of human marrow for the purpose of preventing GvHD in marrow transplantation across MHC differences in man by the use of monoclonal antibodies specific for cell surface molecules unique to T cells in combination with complement. Two such antibodies have been derived, one with specificity for CD2 (sheep red blood cell receptor) and one which defines a novel T cell determinant. The latter antibody precipi- tates a 92 KD molecule and a predominant 45 KD band under non- reducing conditions and reducing conditions, respectively. These two antibodies, in combination with CD7 and CD5 specific antibodies, have been used to carry out studies in human bone marrow T cell depletion. To quantitate T cells remaining in marrow after such depletions, a limiting dilution assay was developed which detects T cells at a level of one T cell per 10-10 marrow cells. A bank of cryopreserved marrows depleted of T cells by a combination of monoclonal antibodies and complement, with the extent of that depletion assessed by limiting dilution assay, has been established and a clinical protocol developed to assess the feasibility of utilizing these marrows in the treatment of aggressive malignancy with marrow ablative combination chemotherapy and radiotherapy.