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急性髓性白血病原始细胞存在下的人T淋巴细胞活化:同种异体刺激的γ干扰素分泌研究

Human T lymphocyte activation in the presence of acute myelogenous leukaemia blasts: studies of allostimulated interferon-gamma secretion.

作者信息

Bruserud O, Mentzoni L, Foss B, Bergheim J, Berentsen S, Nesthus I

机构信息

Medical Department B, University of Bergen, Norway.

出版信息

Cancer Immunol Immunother. 1996 Dec;43(5):275-82. doi: 10.1007/s002620050334.

Abstract

Normal peripheral blood mononuclear cells (PBMC responders) were cultured together with non-irradiated allogeneic PBMC (more than 95% leukaemia blasts) derived from patients with acute leukaemia (referred to as leukaemic PBMC stimulators). Cytokine secretion was determined as cytokine concentrations in supernatants. Both normal PBMC and enriched CD4+ and CD8+ T cells responded to allostimulation with interferon (IFN gamma) secretion. Interleukin-I (IL-1) receptor antagonist and IL-2-neutralizing antibodies decreased IFN gamma secretion. Exogenous IL-1 beta, IL-2 and IL-7 increased allostimulated IFN gamma secretion, whereas decreased levels were seen in the presence of IL-6, IL-10 and granulocyte-colony-stimulating factor (G-CSF). During allorecognition IFN gamma-neutralizing antibodies decreased acute myelogenous leukaemia (AML) blast secretion of G-CSF. We conclude that (i) both CD4+ and CD8+ T cells show allostimulated cytokine secretion in response to allogeneic stimulator cells containing a dominating population of native, cytokine-secreting leukaemia blasts, and (ii) IFN gamma released during this response can modulate the function of allogeneic AML blasts.

摘要

将正常外周血单个核细胞(PBMC反应细胞)与来自急性白血病患者的未照射的同种异体PBMC(超过95%为白血病原始细胞,称为白血病PBMC刺激细胞)共同培养。细胞因子分泌通过上清液中的细胞因子浓度来测定。正常PBMC以及富集的CD4⁺和CD8⁺T细胞对同种异体刺激均有反应,分泌干扰素(IFNγ)。白细胞介素-1(IL-1)受体拮抗剂和IL-2中和抗体可降低IFNγ的分泌。外源性IL-1β、IL-2和IL-7可增加同种异体刺激后的IFNγ分泌,而在存在IL-6、IL-10和粒细胞集落刺激因子(G-CSF)时分泌水平降低。在同种异体识别过程中,IFNγ中和抗体可降低急性髓系白血病(AML)原始细胞G-CSF的分泌。我们得出结论:(i)CD4⁺和CD8⁺T细胞对含有主要为天然的、分泌细胞因子的白血病原始细胞群体的同种异体刺激细胞均表现出同种异体刺激后的细胞因子分泌;(ii)在此反应过程中释放的IFNγ可调节同种异体AML原始细胞的功能。

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