Kinetics and functional implications of Th1 and Th2 cytokine production following activation of peripheral blood mononuclear cells in primary culture

Kinetics and functional implications of Th1 and Th2 cytokine production following activation of peripheral blood mononuclear cells in primary culture
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DOI:
10.1002/eji.1830260612
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发表时间:
1996-06-01
影响因子:
5.4
通讯作者:
Ewan, P
Ewan, P
中科院分区:
医学3区
文献类型:
--
作者:
McHugh, S;Deighton, J;Ewan, P

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细胞因子产生在某些疾病过程中的重要性已被广泛认识。为了研究细胞因子之间的时间关系,我们在体外使用T细胞有丝分裂原植物血凝素(PHA)和各种抗原刺激外周血单个核细胞(PBMC),以诱导主要的Th1(链激酶:链脲酶或纯化蛋白衍生物)或Th2 (pteronyssinus Dermatophagoides pteronsinus,蜜蜂或黄蜂毒:敏感受试者的过敏原)反应。细胞因子的产生用灵敏的生物测定法或酶联免疫吸附法测定。在研究的30名受试者中,10名正常,20名对蝶翼蝶窦(n = 10)或蜂毒(n = 10)过敏(在特异性过敏原免疫治疗前检查)。我们检查了原代培养中产生的一组细胞因子的时间概况。在pha驱动的培养中,细胞因子的产生顺序依次为白细胞介素(IL)-2、IL-4、IL-5、IL-3、干扰素(IFN)- γ、IL-10、IL-6、IL-12和肿瘤坏死因子(TNF)- α。过敏患者对过敏原的反应本质上以Th2为主,产生IL-4、IL-5、IL-6和IL-10, ifn - γ很少或不产生。IL-2、IL-3、tnf - α和IL-12也少量产生。特应性和正常受试者对细菌抗原的反应主要是Th1, ifn - γ、IL-2和tnf - α水平较高。讨论了细胞因子的生产顺序、数量和速度、特征动力学(生产、消耗、稳态调节)和细胞来源的相关性。
The importance of cytokine production in some disease processes is now widely recognized. To investigate temporal relationships between cytokines, we stimulated peripheral blood mononuclear cells (PBMC) in vitro using the T cell mitogen phytohemagglutinin (PHA) and various antigens chosen to induce predominantly Th1 (streptokinase: streptodornase or purified protein derivative) or Th2 (Dermatophagoides pteronyssinus, bee or wasp venom: allergens in sensitive subjects) responses. Cytokine production was measured by sensitive bioassays or enzyme-linked immunosorbent assays. Of the 30 subjects studied, 10 were normal and 20 individuals were allergic to either D. pteronyssinus (n = 10) or bee venom (n = 10) (examined before specific allergen immunotherapy). We examined the temporal profiles of a panel of cytokines produced in prmary culture. In PHA-driven cultures, cytokines were found to be sequentially produced in the order interleukin (IL)-2, IL-4, IL-5, IL-3, interferon (IFN)-gamma, IL-10, IL-6, IL-12 and tumor necrosis factor (TNF)-alpha. The response to allergen in allergic patients was predominantly Th2 in nature, with the production of IL-4, IL-5, IL-6 and IL-10, but little or no IFN-gamma. IL-2, IL-3, TNF-alpha and IL-12 were also produced in low amounts. The response of both atopic and normal subjects to recall bacterial antigens was predominantly Th1, with high levels of IFN-gamma, IL-2 and TNF-alpha. The relevance of the order, amount and speed of production, characteristic kinetics (production, consumption, homeostatic regulation) and the cell source of the cytokines are discussed.