Varney M L, Ino K, Ageitos A G, Heimann D G, Talmadge J E, Singh R K
Department of Pathology and Microbiology, The University of Nebraska Medical Center, Omaha 68198-5660, USA.
J Interferon Cytokine Res. 1999 Apr;19(4):351-60. doi: 10.1089/107999099314054.
Previous reports showed the abnormal activation of immune cells in growth factor-mobilized peripheral blood stem cell (PBSC) products, which might be responsible for depressed T cell responsiveness to mitogens compared with normal peripheral blood mononuclear cells (PBMC). In the present study, the mRNA expression levels of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) were significantly higher in CD4+ and CD8+ T cells from mobilized PBSC products compared with CD4+ and CD8+ cells from normal peripheral blood (PB). The mRNA expression levels of IL-4 and IL-10 were significantly higher in CD8+ compared with CD4+ cells from PBSC products. However, the expression of IL-2 and IFN-gamma mRNA transcripts was similar in the CD4+ and CD8+ T cells from PBSC products. The levels of IL-10, IL-8, and tumor necrosis factor (TNF)-alpha mRNA were also significantly higher in monocytes isolated from PBSC products compared with monocytes isolated from normal PB. Expression of IL-10-specific mRNA in monocytes also was significantly higher than the levels observed in CD8+ cells from PBSC products. We suggest that both CD4+ and CD8+ cells in the PBSC products are highly activated. However, their response to phytohemagglutinin (PHA) mitogenesis is depressed in part because of IL-10 expression by CD8+ cells and monocytes in addition to the higher levels of monocyte-dependent T cell inhibitory activity. These data demonstrate that aberrant IL-10 expression in the CD8+ T cells and monocytes present in PBSC products may represent a possible mechanism of immune dysfunction in patients after high-dose chemotherapy (HDT) and peripheral blood stem cell transplantation (PBSCT).
先前的报告显示，生长因子动员的外周血干细胞（PBSC）产品中免疫细胞存在异常激活，这可能是与正常外周血单个核细胞（PBMC）相比，T细胞对丝裂原反应性降低的原因。在本研究中，与来自正常外周血（PB）的CD4+和CD8+细胞相比，动员的PBSC产品中CD4+和CD8+ T细胞中白细胞介素（IL）-2、IL-4、IL-10和干扰素-γ（IFN-γ）的mRNA表达水平显著更高。与PBSC产品中的CD4+细胞相比，CD8+细胞中IL-4和IL-10的mRNA表达水平显著更高。然而，PBSC产品中CD4+和CD8+ T细胞中IL-2和IFN-γ mRNA转录本的表达相似。与从正常PB中分离的单核细胞相比，从PBSC产品中分离的单核细胞中IL-10、IL-8和肿瘤坏死因子（TNF）-α mRNA的水平也显著更高。单核细胞中IL-10特异性mRNA的表达也显著高于PBSC产品中CD8+细胞中的水平。我们认为，PBSC产品中的CD4+和CD8+细胞均被高度激活。然而，它们对植物血凝素（PHA）促有丝分裂作用的反应部分受到抑制，这是因为除了单核细胞依赖性T细胞抑制活性水平较高外，CD8+细胞和单核细胞还表达IL-10。这些数据表明，PBSC产品中存在的CD8+ T细胞和单核细胞中IL-10的异常表达可能代表了大剂量化疗（HDT）和外周血干细胞移植（PBSCT）后患者免疫功能障碍的一种可能机制。
