Dreger P, Viehmann K, Steinmann J, Eckstein V, Müller-Ruchholtz W, Löffler H, Schmitz N
Second Department of Medicine, University of Kiel, Germany.
Exp Hematol. 1995 Feb;23(2):147-54.
Allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) appears to be an attractive alternative to allogeneic bone marrow transplantation (BMT). However, because vast amounts of potentially graft-vs.-host-reactive T cells are transfused with PBPC grafts, the use of PBPC in the allogeneic setting may be associated with an increased incidence or severity of graft-vs.-host disease (GVHD). To evaluate strategies for prevention of GVHD after PBPC allografting, we have studied T cell depletion (TCD) of G-CSF-mobilized PBPC samples harvested from six healthy donors and from five patients scheduled for autologous PBPC transplantation. Three approaches (CAMPATH-1 plus autologous complement [C], immunomagnetic CD34+ cell selection, and biotin-avidin-mediated CD34+ cell selection) were compared. TCD of PBPC samples with the monoclonal antibody (MAb) CAMPATH-1 plus autologous C resulted in a median elimination of 2.16 log CD3+ T cells, whereas 39% of CD56+ natural killer (NK) cells and 56% of CD34+ progenitor cells were recovered. TCD by CD34+ cell selection with the Isolex (Baxter, Munich, Germany) or Ceprate (CellPro, Bothell, WA) devices achieved median depletions (Isolex vs. Ceprate) of 4.04 vs. 3.12 log T cells and > 5 vs. 3.27 log NK cells while allowing the recovery of 36 vs. 27% CD34+ cells. The median purity of CD34+ cells in the final product was 1.7 (CAMPATH-1), 94 (Isolex), and 65% (Ceprate). We conclude that all methods tested effectively deplete T cells from PBPC preparations harvested from healthy donors. Whereas immunomagnetic CD34+ selection is most effective in terms of elimination of T cells, the less intensive T and NK cell depletions achieved with CAMPATH-1 might be advantageous with regard to retaining engraftment potential and graft-vs.-leukemia (GVL) activity of PBPC allografts.
粒细胞集落刺激因子（G-CSF）动员的外周血祖细胞（PBPC）的异基因移植似乎是异基因骨髓移植（BMT）的一个有吸引力的替代方案。然而，由于大量潜在的移植物抗宿主反应性T细胞随PBPC移植物一起输注，在异基因环境中使用PBPC可能与移植物抗宿主病（GVHD）的发生率增加或严重程度增加有关。为了评估PBPC同种异体移植后预防GVHD的策略，我们研究了从6名健康供体和5名计划进行自体PBPC移植的患者中采集的G-CSF动员的PBPC样本的T细胞清除（TCD）情况。比较了三种方法（CAMPATH-1加自体补体[C]、免疫磁珠CD34+细胞分选和生物素-抗生物素蛋白介导的CD34+细胞分选）。用单克隆抗体（MAb）CAMPATH-1加自体补体对PBPC样本进行TCD，导致CD3+T细胞中位数清除2.16 log，而39%的CD56+自然杀伤（NK）细胞和56%的CD34+祖细胞得以恢复。使用Isolex（德国慕尼黑百特公司）或Ceprate（美国华盛顿州博塞尔CellPro公司）设备通过CD34+细胞分选进行TCD，T细胞中位数清除率（Isolex对Ceprate）分别为4.04 log和3.12 log，NK细胞清除率分别>5 log和3.27 log，同时CD34+细胞回收率分别为36%和27%。最终产物中CD34+细胞的中位数纯度分别为1.7%（CAMPATH-1）、94%（Isolex）和65%（Ceprate）。我们得出结论，所有测试方法均能有效清除健康供体采集的PBPC制剂中的T细胞。就T细胞清除而言，免疫磁珠CD34+分选最为有效，而CAMPATH-1实现的强度较低的T细胞和NK细胞清除在保留PBPC同种异体移植物植入潜力和移植物抗白血病（GVL）活性方面可能具有优势。
