Lonial Sagar, Hicks Michelle, Rosenthal Hilary, Langston Amelia, Redei Istvan, Torre Claire, Duenzl Mary, Feinstein Bonita, Cherry Judith, Waller Edmund K
Winship Cancer Institute, Emory University School of Medicine, 1365 Clifton Road, Atlanta, GA 30322, USA.
Biol Blood Marrow Transplant. 2004 Dec;10(12):848-57. doi: 10.1016/j.bbmt.2004.07.008.
The ability of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration to increase the content of blood leucocytes and hematopoietic progenitor cells (HPCs) is well established, yet the effect of these cytokines on immune function is less well described. Recent data indicate that plasmacytoid dendritic cells (DC2) may inhibit cellular immune response. We hypothesized that administration of the combination of G-CSF and GM-CSF after chemotherapy would reduce the type 2, or plasmacytoid, DC2 content of the autologous blood HPC grafts compared with treatment with G-CSF alone. To test this hypothesis, 35 patients with lymphoma and myeloma were randomized to receive either G-CSF or the combination of G-CSF plus GM-CSF after chemotherapy, and blood HPC grafts were collected by apheresis. Cytokine-related adverse events between the 2 groups were similar. More than 2 x 10(6)CD34 + cells per kilogram were collected by apheresis in 14 of 18 subjects treated with G-CSF and in 16 of 17 subjects treated with GM-CSF plus G-CSF ( p = not significant). There were minor differences between the 2 groups with respect to the content of T cells and CD34 + cells in the apheresis products. However, grafts collected from recipients of the combination of GM-CSF plus G-CSF had significantly fewer DC2 cells and similar numbers of DC1 cells compared with recipients treated with G-CSF alone. A third cohort of patients received chemotherapy followed by the sequential administration of G-CSF and the addition of GM-CSF 6 days later. Grafts from these patients had a markedly reduced DC2 content compared with those from patients treated either with G-CSF alone or with the concomitant administration of both cytokines. These data, and recent data that cross-presentation of antigen by DC2 cells may induce antigen-specific tolerance among T cells, suggest that GM-CSF during mobilization of blood HPC grafts may be a clinically applicable strategy to enhance innate and acquired immunity after autologous and allogeneic HPC transplantation.
粒细胞集落刺激因子（G-CSF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）给药可增加血液白细胞和造血祖细胞（HPC）含量，这一点已得到充分证实，但这些细胞因子对免疫功能的影响描述较少。近期数据表明，浆细胞样树突状细胞（DC2）可能抑制细胞免疫反应。我们假设，与单独使用G-CSF治疗相比，化疗后联合使用G-CSF和GM-CSF会降低自体血液HPC移植物中2型或浆细胞样DC2的含量。为验证这一假设，35例淋巴瘤和骨髓瘤患者在化疗后被随机分为接受G-CSF组或G-CSF加GM-CSF联合组，通过单采术采集血液HPC移植物。两组细胞因子相关不良事件相似。接受G-CSF治疗的18名受试者中有14名、接受GM-CSF加G-CSF治疗的17名受试者中有16名通过单采术采集到每千克超过2×10⁶个CD34⁺细胞（p值无统计学意义）。两组单采术产品中T细胞和CD34⁺细胞含量存在微小差异。然而，与单独接受G-CSF治疗的受试者相比，接受GM-CSF加G-CSF联合治疗的受试者采集的移植物中DC2细胞明显减少，而DC1细胞数量相似。第三组患者接受化疗，随后序贯给予G-CSF，并在6天后加用GM-CSF。与单独接受G-CSF治疗或同时给予两种细胞因子治疗的患者相比，这些患者的移植物中DC2含量明显降低。这些数据，以及近期关于DC2细胞交叉呈递抗原可能诱导T细胞间抗原特异性耐受的数据表明，在血液HPC移植物动员过程中使用GM-CSF可能是一种临床上可行的策略，可增强自体和异基因HPC移植后的固有免疫和获得性免疫。
