Mills K C, Gross T G, Varney M L, Heimann D G, Reed E C, Kessinger A, Talmadge J E
Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Bone Marrow Transplant. 1996 Jul;18(1):53-61.
The T cell-mediated antineoplastic activity observed following allogeneic transplantation and the suggestion of improved therapeutic efficacy by autologous peripheral stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) stimulated our interest in the immunologic competence of stem cell products. We report the immune phenotype and function of normal peripheral blood (PB) cells, bone marrow (BM) cells from normal donors and cancer bearing patients, GM-CSF-mobilized and apheresed blood mononuclear cells from NHL patients, unmobilized apheresed mononuclear cells from normal volunteers and umbilical cord blood (CB). The analyses include three-color fluorescent cytometry of the major hematologic and immunologic phenotypes as well as natural killer (NK) activity, natural suppressor (NS) activity, and phytohemagglutinin (PHA) and pokeweed (PWM) mitogenesis. These studies demonstrated an increased frequency of T cells in apheresis products as compared to BM and CB products. Specifically, the mobilized PSC had significant increases in CD3+, CD4+, CD45RO+ and CD56+ cells relative to BM cells. In addition, the frequency of TCR gamma/delta + cells in all the stem cell products, with the exception of CB, were also increased compared to normal peripheral blood leukocytes (PBL). However, all the stem cell products had a significant depression in T (PHA mitogenesis) and B (PWM mitogenesis) cell function. The depression in immune cell functionality, in the PSC products was perhaps due to the high frequency of monocytes which appeared to be increased due to both mobilization and apheresis. The frequency of the NK cell phenotype (CD56) but not function was increased in the mobilized PSC products, while the NK cell function in the BM products from cancer patients but not normal donors was depressed as compared to normal PBL. In summary, there are significant differences in the cellular phenotypes and immunologic competence among the various stem cell products with potential therapeutic implications.
同种异体移植后观察到的T细胞介导的抗肿瘤活性,以及与自体骨髓移植(ABMT)相比,自体外周干细胞移植(PSCT)对非霍奇金淋巴瘤(NHL)治疗效果改善的提示,激发了我们对干细胞产品免疫能力的兴趣。我们报告了正常外周血(PB)细胞、正常供体和癌症患者的骨髓(BM)细胞、NHL患者经粒细胞集落刺激因子(GM-CSF)动员和采集的血液单核细胞、正常志愿者未动员采集的单核细胞以及脐带血(CB)的免疫表型和功能。分析包括主要血液学和免疫学表型的三色荧光细胞术,以及自然杀伤(NK)活性、自然抑制(NS)活性、植物血凝素(PHA)和商陆(PWM)促有丝分裂作用。这些研究表明,与BM和CB产品相比,采集产品中T细胞的频率增加。具体而言,相对于BM细胞,动员的PSC中CD3 +、CD4 +、CD45RO +和CD56 +细胞显著增加。此外,除CB外,所有干细胞产品中TCRγ/δ +细胞的频率相对于正常外周血白细胞(PBL)也有所增加。然而,所有干细胞产品的T(PHA促有丝分裂作用)和B(PWM促有丝分裂作用)细胞功能均显著降低。PSC产品中免疫细胞功能的降低可能是由于单核细胞频率较高,这似乎是由于动员和采集导致的。动员的PSC产品中NK细胞表型(CD56)的频率增加,但功能未增加,而癌症患者而非正常供体的BM产品中的NK细胞功能与正常PBL相比降低。总之,各种干细胞产品在细胞表型和免疫能力方面存在显著差异,具有潜在的治疗意义。