Talmadge J E, Reed E C, Kessinger A, Kuszynski C A, Perry G A, Gordy C L, Mills K C, Thomas M L, Pirruccello S J, Letheby B A, Arneson M A, Jackson J D
Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Bone Marrow Transplant. 1996 Jan;17(1):101-9.
The immunologic attributes of cytokine mobilized peripheral blood stem cell (PSC) products (n = 52) and the resulting reconstitution of the hematopoietic and immunologic system following autologous transplantation were examined in a consecutive population of non-Hodgkin lymphoma (NHL), or solid tumor patients at the University of Nebraska Medical Center. Granulocyte-monocyte colony stimulating factor (GM-CSF)-mobilized PSC products had a high frequency of monocytes (31%) and bands (15%) as compared to normal peripheral blood (PB) cells. The phenotypic analysis of the mobilized PSC product revealed that they had normal levels of CD4+ cells, an increased frequency of CD8+ cells and a corresponding decrease in the CD4+:CD8+ cell ratio as compared to the peripheral blood leukocytes (PBL) of normal individuals. PSC products also had an increase in CD34+ cells as compared to PB. Natural killer (NK) and T cell activity in the PSC products were also lower than that observed in PB. Post-transplantation there was an accelerated reconstitution of NK-cell function in the PB as compared to T cell function (PHA (phytohemagglutinin) mitogenesis) which did not return to normal by day 100 post-transplantation. We also report for the first time high levels of an irradiation resistant suppressor cell activity in the PSC product and in the PB post-transplantation. There was also a concomitant increase in CD4-, CD8-, TCR alpha/beta+ cells (phenotypic homolog of 'natural suppressor' (NS) cells) in the PB post-transplantation. The number of months of prior chemotherapy correlated with PHA response but the NS activity and frequency of CD4-, CD8- and TCR alpha/beta+ cells did not. Further, cytokine mobilization and apheresis appears to contribute to the loss of PHA responsiveness and the increased levels of suppressor cell activity.
在内布拉斯加大学医学中心,对连续的非霍奇金淋巴瘤(NHL)或实体瘤患者群体,检测了细胞因子动员的外周血干细胞(PSC)产品(n = 52)的免疫学特性,以及自体移植后造血和免疫系统的重建情况。与正常外周血(PB)细胞相比,粒细胞-单核细胞集落刺激因子(GM-CSF)动员的PSC产品中单核细胞频率较高(31%),杆状核细胞频率较高(15%)。对动员的PSC产品进行表型分析发现,与正常个体的外周血白细胞(PBL)相比,它们的CD4+细胞水平正常,CD8+细胞频率增加,CD4+:CD8+细胞比值相应降低。与PB相比,PSC产品中的CD34+细胞也有所增加。PSC产品中的自然杀伤(NK)细胞和T细胞活性也低于PB中的观察值。移植后,与T细胞功能(植物血凝素(PHA)促有丝分裂)相比,PB中NK细胞功能的重建加速,移植后100天仍未恢复正常。我们还首次报道了PSC产品和移植后PB中高水平的辐射抗性抑制细胞活性。移植后PB中CD4-、CD8-、TCRα/β+细胞(“自然抑制”(NS)细胞的表型同源物)也相应增加。既往化疗的月数与PHA反应相关,但NS活性以及CD4-、CD8-和TCRα/β+细胞的频率与之无关。此外,细胞因子动员和单采似乎导致了PHA反应性的丧失以及抑制细胞活性水平的增加。