Cederblad B, Blomberg S, Vallin H, Perers A, Alm G V, Rönnblom L
Division of Immunology, Swedish University of Agricultural Sciences.
J Autoimmun. 1998 Oct;11(5):465-70. doi: 10.1006/jaut.1998.0215.
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 (NIPC), 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 co-stimulated 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.
系统性红斑狼疮（SLE）患者常常持续产生α干扰素（IFN-α），但外周血单个核细胞（PBMC）体外产生IFN-α的能力可能会不同程度降低。我们在此报告，单纯疱疹病毒（HSV）在类似未成熟树突状细胞的PBMC中诱导产生的IFN-α，即所谓的天然IFN-α产生细胞（NIPC），比仙台病毒（SV）在单核细胞中诱导产生的IFN-α受到的影响更大。在细胞水平上，HSV激活的NIPC频率降低了70倍，但残余的NIPC产生的IFN-α量正常（1 - 2 U/细胞）。当受到IFN-α-γ和GM-CSF联合刺激时，SLE-PBMC中的NIPC频率增加了10倍，而对照PBMC中则没有增加。在SLE患者中未检测到PBMC自发产生IFN-α。虽然未发现SLE血清中有抑制IFN-α产生的因子，但11例SLE患者中有4例的血清能诱导健康对照PBMC产生IFN-α。我们推测，SLE患者血液中NIPC数量减少是因为被招募到组织并被内源性IFN-α诱导剂激活，以及缺乏共刺激细胞因子。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。
