Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-α-producing cells
Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-α-producing cells
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DOI：
10.1006/jaut.1998.0215
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发表时间：
1998-10-01
影响因子：
12.8
通讯作者：
Ronnblom, L
中科院分区：
文献类型：
--
作者：
Cederblad, B;Blomberg, S;Ronnblom, L
系统性红斑狼疮（SLE）患者经常持续产生干扰素-α（IFN-α），但外周血单核细胞（PBMC）的体外IFN-α产生可能不同程度地减少。我们在这里报告，在PBMC中，由单纯疱疹病毒（HSV）诱导的IFN-α产生类似于未成熟的树突状细胞和指定的天然IFN-α产生细胞（NPPC），比仙台病毒（SV）诱导的单核细胞更受影响。在细胞水平，HSV激活的NIPC的频率降低了70倍，但残留的NIPC产生正常量的IFN-α（1-2 U/细胞）。当IFN-α、-γ和GM-CSF联合刺激时，SLE PBMC中的NIPC频率增加10倍，而对照PBMC中没有。在SLE患者中未检测到PBMC自发产生IFN-α。虽然没有观察到抑制IFN-α产生的SLE血清因子，但11名SLE患者中有4名患者的血清诱导了健康对照PBMC中IFN-α的产生。我们认为，SLE患者血液中NIPC的数量减少是因为内源性IFN-α诱导剂对组织的募集和激活，以及缺乏共刺激细胞因子。在SLE中产生的IFN-α可能具有致病意义，因为在IFN-α治疗期间，感染或肿瘤患者会发生自身免疫性疾病。(C)1998学术出版社
Systemic lupus erythematosus (SLE) patients often have continuous production of interferon-alpha (IFN-alpha), but production of in vitro IFN-alpha by peripheral blood mononuclear cells (PBMC) may be varyingly reduced. We here report that IFN-alpha production induced by Herpes simplex virus (HSV) in PBMC resembling immature dendritic cells and designated natural IFN-alpha producing cells (NPPC), was much more affected than that induced by sendai virus (SV) in monocytes. At the cell level, the frequency of HSV-activated NIPC was reduced 70-fold, but residual NIPC produced normal amounts of IFN-alpha (1-2 U/cell). The NIPC frequency increased 10-fold in SLE-PBMC, but not in control PBMC, when costimulated by the combination IFN-alpha, -gamma and GM-CSF. No spontaneous IFN-alpha production by PBMCs was detected in SLE patients. While no SLE serum factor inhibiting IFN-alpha production was seen, sera of four out of 11 SLE patients induced IFN-alpha production in healthy control PBMC. We propose that the number of NIPC in SLE are reduced in blood because of recruitment to tissues and activation by an endogenous IFN-alpha inducer, as well as because of lack of co-stimulatory cytokines. IFN-alpha produced in SLE could be of pathogenic significance, because autoimmune diseases develop in patients with infections or tumours during IFN-alpha therapy. (C) 1998 Academic Press