Bruserud O, Pawelec G
Medical Department B, Haukeland University Hospital, Bergen, Norway.
Cancer Immunol Immunother. 1996 Mar;42(3):133-40. doi: 10.1007/s002620050263.
T cell clones (CD4+CD8-TCR alpha beta+gamma delta- derived from bone marrow transplant recipients were stimulated with phytohaemagglutinin (PHA) +interleukin-2 (IL-2) in the presence of irradiated (50 Gy) peripheral blood mononuclear cells (PBMC) derived from acute Leukaemia patients (leukaemic PBMC containing more than 95% blast cells). Leukaemic PBMC could function as accessory cells during mitogenic T cell activation resulting in both T cell proliferation and a broad T cell cytokine response [IL-3, IL-4, IL-10, granulocyte/macrophage-colony-stimulating factor (GM-CSF) tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) secretion]. Blockade of IL-1 effects by adding IL-1 receptor antagonist together with PHA + IL-2 + leukaemia blasts increased T cell proliferation, whereas IL-6-neutralizing antibodies did not alter T cell proliferation. A qualitatively similar T cell cytokine response and a similar cytokine profile (highest levels detected for GM-CSF and IFN gamma) were detected when normal polyclonal T cell lines were stimulated with PHA in the presence of non-irradiated leukaemic PBMC. When leukaemic PBMC derived from 18 acute myelogenous leukaemia patients were cultured with PHA and cells from a polyclonal T cell line, increased concentrations of the T cell cytokines IFN gamma and IL-4 were detected for all patients. We conclude that T cell activation resulting in proliferation and a broad cytokine response can take place in the presence of excess acute myelogenous leukaemia blasts.
用植物血凝素(PHA)+白细胞介素-2(IL-2)在来自急性白血病患者的经辐照(50 Gy)的外周血单个核细胞(PBMC)(白血病PBMC含超过95%原始细胞)存在的情况下刺激从骨髓移植受者获得的T细胞克隆(CD4+CD8-TCRαβ+γδ-)。白血病PBMC在有丝分裂原性T细胞激活过程中可作为辅助细胞,导致T细胞增殖和广泛的T细胞细胞因子反应[IL-3、IL-4、IL-10、粒细胞/巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子α(TNFα)和干扰素γ(IFNγ)分泌]。通过将IL-1受体拮抗剂与PHA+IL-2+白血病原始细胞一起添加来阻断IL-1的作用可增加T细胞增殖,而IL-6中和抗体不会改变T细胞增殖。当正常多克隆T细胞系在未辐照的白血病PBMC存在的情况下用PHA刺激时,检测到定性相似的T细胞细胞因子反应和相似的细胞因子谱(检测到GM-CSF和IFNγ的最高水平)。当来自18例急性髓性白血病患者的白血病PBMC与PHA和来自多克隆T细胞系的细胞一起培养时,所有患者均检测到T细胞细胞因子IFNγ和IL-4的浓度增加。我们得出结论,在存在过量急性髓性白血病原始细胞的情况下可发生导致增殖和广泛细胞因子反应的T细胞激活。