Ozer H, Han T, Early A, O'Leary M, Thompson D, Dadey B, Cohen N, Higby D J
Cancer Drug Deliv. 1983;1(1):79-86. doi: 10.1089/cdd.1983.1.79.
Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation is the most significant limiting factor preventing the widespread application of transplant therapy in acute leukemia and aplastic anemia. GVHD is mediated by T cells that contaminate harvested marrow in proportions ranging from 5-50% of the mononuclear cell population. T cell depletion (TCD) of large volumes of human marrow by E-rosetting for 24 h at 4 degrees C with modified sheep erythrocytes achieves removal of greater than or equal to 97% of all T cells, as judged by cytofluorographic analysis of the T-depleted bone marrow population with a broad panel of anti-T cell monoclonal antibodies, and abrogates functional T cell activity. Although T-depleted bone marrow cell recoveries were 2 logs below total harvested buffy coat cell numbers, the TCD mononuclear population was more than 99% viable and was enriched twofold for Ia+ cells as judged by cytofluorographic analysis. This method is at least the equivalent of those employing lectin column or monoclonal antibody/complement lysis techniques and is simpler to perform. Successful engraftment of adult patients can safely be obtained with as few as 4 X 10(8) total mononuclear cells following the 24-h procedure suggesting that prolonged or repeated T-depletion procedures do not interfere with stem cell engraftment. Preliminary results suggest that this method of TCD may ameliorate GVHD in histoincompatible transplants.
异基因骨髓移植后的急性移植物抗宿主病（GVHD）是限制移植疗法在急性白血病和再生障碍性贫血中广泛应用的最重要因素。GVHD由污染采集骨髓的T细胞介导，其在单核细胞群体中的比例为5%-50%。通过在4℃下用改良的绵羊红细胞进行E花环试验24小时，对大量人骨髓进行T细胞清除（TCD），通过用一组广泛的抗T细胞单克隆抗体对T细胞清除后的骨髓群体进行细胞荧光分析判断，可去除大于或等于97%的所有T细胞，并消除功能性T细胞活性。尽管T细胞清除后的骨髓细胞回收率比采集的总血沉棕黄层细胞数低2个对数，但通过细胞荧光分析判断，TCD单核细胞群体的存活率超过99%，并且Ia+细胞富集了两倍。该方法至少与采用凝集素柱或单克隆抗体/补体裂解技术的方法相当，且操作更简单。在24小时程序后，仅用低至4×10⁸个总单核细胞就能安全地使成年患者成功植入，这表明延长或重复的T细胞清除程序不会干扰干细胞植入。初步结果表明，这种TCD方法可能会改善组织不相容移植中的GVHD。
