Arpinati Mario, Chirumbolo Gabriella, Urbini Benedetta, Bonifazi Francesca, Bandini Giuseppe, Saunthararajah Yogen, Zagnoli Alessandra, Stanzani Marta, Falcioni Sadia, Perrone Giulia, Tura Sante, Baccarani Michele, Rondelli Damiano
Research Center for Transplant Immunology, Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Italy.
Biol Blood Marrow Transplant. 2004 Feb;10(2):106-15. doi: 10.1016/j.bbmt.2003.09.005.
Human dendritic cells (DC) comprise 2 subsets-plasmacytoid CD123(+) and myeloid CD11c(+) DC-that may have distinct roles in the regulation of immunity after allogeneic hematopoietic stem cell transplantation. In this study, we analyzed the kinetics of CD123(+) DC and CD11c(+) DC reconstitution in 31 patients who underwent transplantation with allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells from HLA-identical sibling donors after myeloablative conditioning. Lineage marker-negative HLA-DR(+) CD11c(+) CD11c(+) DC and lineage marker-negative HLA-DR(+) CD123(+) CD123(+) DC, as well as monocytes and lymphoid subsets, were enumerated in donor grafts and in the PB of patients at various time points after transplantation. Reconstitution of both CD11c(+) DC and CD123(+) DC to normal levels occurred within 6 to 12 months and was not affected by the diagnosis, preparatory regimen, or graft composition. However, PB CD11c(+) DC and CD123(+) DC counts were significantly reduced in patients with acute GVHD grade II to IV (at 1 and 3 months) and grade I (at 1 month). Patients with chronic GVHD instead showed reduced CD123(+) DC counts only 6 months after transplantation. Moreover, treatment with steroids (>0.1 mg/kg) was significantly associated with reduced PB CD11c(+) DC and CD123(+) DC counts at all time points after transplantation. In multivariate analysis, only acute GVHD affected DC reconstitution early after transplantation. These results will prompt new studies addressing whether DC reconstitution correlates with immunity against infectious agents or with graft-versus-tumor reactions after PB stem cell allotransplantation.
人类树突状细胞（DC）由两个亚群组成，即浆细胞样CD123(+) DC和髓样CD11c(+) DC，它们在异基因造血干细胞移植后的免疫调节中可能具有不同作用。在本研究中，我们分析了31例接受清髓性预处理后移植来自 HLA 相同同胞供者的异基因粒细胞集落刺激因子动员外周血（PB）干细胞的患者中CD123(+) DC和CD11c(+) DC重建的动力学。在移植后的不同时间点，对供者移植物和患者外周血中的谱系标志物阴性HLA-DR(+) CD11c(+) CD11c(+) DC、谱系标志物阴性HLA-DR(+) CD123(+) CD123(+) DC以及单核细胞和淋巴细胞亚群进行计数。CD11c(+) DC和CD123(+) DC均在6至12个月内恢复至正常水平，且不受诊断、预处理方案或移植物组成的影响。然而，急性移植物抗宿主病（GVHD）II至IV级患者（在1个月和3个月时）以及I级患者（在1个月时）的外周血CD11c(+) DC和CD123(+) DC计数显著降低。相反，慢性GVHD患者仅在移植后6个月出现CD123(+) DC计数降低。此外，移植后所有时间点使用类固醇（>0.1 mg/kg）治疗均与外周血CD11c(+) DC和CD123(+) DC计数降低显著相关。多因素分析显示，仅急性GVHD在移植后早期影响DC重建。这些结果将促使开展新的研究，探讨PB干细胞同种异体移植后DC重建是否与抗感染免疫或移植物抗肿瘤反应相关。
