Russell Athena, Malik Sunita, Litzow Mark, Gastineau Dennis, Roy Vivek, Zubair Abba C
Transfusion Medicine, Department of Pathology, Jacksonville, Florida.
Division of Hematology/Oncology, Mayo Clinic, Rochester, Minnesota.
Transfusion. 2015 Jul;55(7):1758-65; quiz 1757. doi: 10.1111/trf.13073. Epub 2015 Mar 11.
Poor marrow cellularity alone cannot explain poor hematopoietic progenitor cell (HPC) mobilization. This study assessed the role of CD8+ T cells in HPC cell mobilization and engraftment.
Mobilization and engraftment were assessed in 192 autologous HPC donors. CD34+, CD4+, and CD8+ T-cell contents in apheresis products were evaluated. Using a chemotaxis assay, we assessed the effect of purified autologous CD8+ T cells from low and high mobilizers on HPC migration from high to low stromal cell-derived factor (SDF-1α) concentration gradients. We also assessed CD8+ T-cell content association with days to neutrophil engraftment.
The median number of CD34+ cells/kg was 4.7 × 10(6) . Patients were categorized according to their total CD34+ cell collection quartile distribution into low, moderate, and high mobilizers. We found that HPC products from low mobilizers contained more CD8+ T cells than HPC products from moderate and high mobilizers. Chemotaxis assays showed depletion of CD8+ T cells enhances HPC mobilization independent of SDF-1α concentration. Neutrophil engraftment analysis showed that the higher the CD8+ T-cell content per unit CD34+ cell, the faster the rate of engraftment.
Our findings suggest CD8+ T cells inhibit HPC mobilization and facilitate homing and engraftment.
单纯骨髓细胞减少无法解释造血祖细胞(HPC)动员不佳的情况。本研究评估了CD8 + T细胞在HPC细胞动员和植入中的作用。
对192例自体HPC供者的动员和植入情况进行评估。评估单采产品中CD34 +、CD4 +和CD8 + T细胞含量。使用趋化试验,我们评估了来自低动员者和高动员者的纯化自体CD8 + T细胞对HPC从高到低基质细胞衍生因子(SDF-1α)浓度梯度迁移的影响。我们还评估了CD8 + T细胞含量与中性粒细胞植入天数的相关性。
CD34 +细胞/kg的中位数为4.7×10⁶。根据其总CD34 +细胞采集四分位数分布将患者分为低、中、高动员者。我们发现,低动员者的HPC产品比中、高动员者的HPC产品含有更多的CD8 + T细胞。趋化试验表明,CD8 + T细胞的消耗可增强HPC动员,且与SDF-1α浓度无关。中性粒细胞植入分析表明,每单位CD34 +细胞中CD8 + T细胞含量越高,植入速度越快。
我们的研究结果表明,CD8 + T细胞抑制HPC动员,并促进归巢和植入。