Chen Benny J, Cui Xiuyu, Sempowski Gregory D, Domen Jos, Chao Nelson J
Bone Marrow Transplantation Program, Department of Medicine, Human Vaccine Institute, Duke University Medical Center, Box 3289, 250 Carl Building, Durham, NC 27710, USA.
Blood. 2004 Jun 1;103(11):4344-52. doi: 10.1182/blood-2003-07-2534. Epub 2004 Feb 19.
In the current study, we tested whether higher numbers of hematopoietic stem cells correlate with the speed of immune reconstitution in a congenic transplantation model (C57BL/Ka, CD45.1, Thy1.1-->C57BL/6, CD45.2, Thy1.2) using purified hematopoietic stem cells (c-Kit(+)Thy1.1(low)Lin(-/low)Sca-1(+)). There were 3 different doses of stem cells used (400, 1000, and 5000). Phenotypic analyses in peripheral blood and spleen demonstrated that higher numbers of infused stem cells are associated with more rapid regeneration of T cells (CD4(+), CD8(+), naive CD4(+), naive CD8(+)) and B cells at early time points. The numbers of T and B cells eventually became equivalent between different dose groups at late time points. Production of interleukin-2 and inter-feron-gamma per T cell was similar regardless of stem cell dose even when tested at the time when there were significant differences in peripheral T-cell counts. The improved immune recovery was attributed to a more rapid regeneration of donor-type immune cells. Higher numbers of total thymocytes and signal joint T-cell receptor excision circles were observed in the higher dose stem cell recipients, suggesting that accelerated regeneration of T cells was due to enhanced thymopoiesis.
在当前研究中，我们使用纯化的造血干细胞（c-Kit(+)Thy1.1(low)Lin(-/low)Sca-1(+)），在同基因移植模型（C57BL/Ka，CD45.1，Thy1.1→C57BL/6，CD45.2，Thy1.2）中测试了造血干细胞数量增加是否与免疫重建速度相关。使用了3种不同剂量的干细胞（400、1000和5000）。外周血和脾脏的表型分析表明，在早期，注入的干细胞数量增加与T细胞（CD4(+)、CD8(+)、初始CD4(+)、初始CD8(+)）和B细胞的更快再生相关。在后期，不同剂量组之间T细胞和B细胞的数量最终变得相当。无论干细胞剂量如何，每个T细胞产生白细胞介素-2和干扰素-γ的情况都是相似的，即使在外周T细胞计数存在显著差异时进行检测也是如此。免疫恢复的改善归因于供体型免疫细胞的更快再生。在接受高剂量干细胞的受体中观察到总胸腺细胞数量和信号联合T细胞受体切除环增加，这表明T细胞的加速再生是由于胸腺生成增强。
