Abnormal regulation of interferon-γ, interleukin-12, and tumor necrosis factor-α in human interferon-γ receptor 1 deficiency
Abnormal regulation of interferon-γ, interleukin-12, and tumor necrosis factor-α in human interferon-γ receptor 1 deficiency
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DOI：
10.1086/515670
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发表时间：
1998-10-01
影响因子：
6.4
通讯作者：
Fleisher, TA
中科院分区：
文献类型：
--
作者：
Holland, SM;Dorman, SE;Fleisher, TA
分枝杆菌感染是由干扰素-γ(干扰素-γ)及其所阐述的细胞反应严格控制的，如干扰素-γ受体配体结合链(干扰素-γR1)突变的患者传播非结核分枝杆菌感染所表明的那样。2例来自印度次大陆的无关患者出现了新的纯合子隐性干扰素-γR1突变，其免疫后遗症表现为干扰素-γR1缺乏症。在体外，这些患者的外周血单个核细胞在植物血凝素(PHA)的作用下产生10%的正常干扰素-γ和白介素12(IL-12)，但在PHA+IL-12的作用下产生正常数量的干扰素-γ。肿瘤坏死因子-α(TNF-α)的产生在内毒素和PHA的反应下是正常的，但不能因加入干扰素-γ而增加，在杂合子患者亲属中未发现异常表型。这些患者证明了干扰素-γ受体在干扰素-γ、IL-12和肿瘤坏死因子-α的调节中所起的关键作用。
Mycobacterial infections are critically controlled by interferon-gamma (IFN-gamma) and the cellular responses it elaborates, as shown by patients with mutations in the IFN-gamma receptor ligand-binding chain (IFN-gamma R1) who have disseminated nontuberculous mycobacterial infections. The immunologic sequelae of IFN-gamma R1 deficiency were characterized in 2 unrelated patients from the Indian subcontinent with novel homozygous recessive IFN-gamma R1 mutations. In vitro, these patients' peripheral blood mononuclear cells produced 10% of normal IFN-gamma and interleukin-12 (IL-12) in response to phytohemagglutinin (PHA) but normal amounts of IFN-gamma in response to PHA plus IL-12. Tumor necrosis factor-alpha (TNF-alpha) production was normal in response to endotoxin and to PHA but was not augmented by the addition of IFN-gamma, An abnormal phenotype was not found in heterozygous patient relatives. These patients demonstrate the critical role that the IFN-gamma receptor plays in the regulation of IFN-gamma, IL-12, and TNF-alpha.