Signals involved in the early TH1/TH2 polarization of an immune response depending on the type of antigen
Signals involved in the early TH1/TH2 polarization of an immune response depending on the type of antigen
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DOI：
10.1016/s0091-6749(99)70505-1
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发表时间：
1999-02-01
影响因子：
14.2
通讯作者：
Saloga, J
中科院分区：
文献类型：
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作者：
Bellinghausen, I;Brand, U;Saloga, J
背景：表皮细胞 (EC) 响应抗原暴露而早期产生不同的细胞因子，可能控制 T-H1 样免疫反应（例如接触敏感性）或 T-H2 样免疫反应（例如 IgE 依赖性即时过敏）的发展，具体取决于抗原的类型。 目的：本研究的目的是比较蛋白质过敏原诱导的信号与 EC 中以及随后在局部引流淋巴结细胞中由半抗原诱导的信号。方法：BALB/c小鼠仅在体内分别用蛋白过敏原卵清蛋白或桦树花粉或半抗原2,4-二硝基氟苯或三硝基氯苯进行引发，并在与EC体外共培养后通过ELISA测量响应脾细胞的细胞因子和免疫球蛋白分泌。通过逆转录酶 PCR 分析 EC 和 LNC 中细胞因子 mRNA 表达的诱导。结果：在蛋白质过敏原存在的情况下，EC 增强 T-H2 免疫反应的诱导（脾细胞产生 IL-4 和 IgE），而 T-H1 免疫反应（IFN-gamma 和 IgG(2a) 产生）仅在半抗原的情况下被诱导。卵清蛋白的热失活并没有减弱 T-H2 免疫反应的发展。抗原对 EC 的直接影响之一是在体外用蛋白过敏原刺激（30 分钟）比用半抗原刺激（2 小时）后 IL-10 mRNA 更早表达。通过使用体内方法，用三硝基氯苯而非卵清蛋白使皮肤致敏，导致 LNC 中早期诱导 IL-1 beta、IL-12p40 和 IFN-gamma mRNA，而 IL-18 则由两者诱导。结论：这些数据表明，抗原类型通过引发上皮中已有的不同信号，强烈影响免疫反应的类型。
Background: The early production of distinct cytokines by epidermal cells (ECs) in response to antigen exposure may govern the development of T-H1-like immune responses, such as contact sensitivity, or T-H2-like immune responses, such as IgE-dependent allergies of the immediate type, depending on the type of antigen.Objective: The aim of this study was to compare the signals induced by protein allergens with those induced by haptens in ECs and subsequently in local draining lymph node cells (LNCs) or splenocytes.Methods: BALB/c mice mere primed in vivo with the protein allergens ovalbumin or birch pollen or the haptens 2,4-dinitrofluorobenzene or trinitrochlorbenzene, respectively, and cytokine and immunoglobulin secretions of responding splenocytes were measured by ELISA after in vitro coculture with ECs. Induction of cytokine mRNA expression in ECs and LNCs was analyzed by reverse transcriptase-PCR.Results: In the presence of protein allergens, ECs enhance the induction of a T-H2 immune response (IL-4 and IgE production of splenocytes), whereas a T-H1 immune response (IFN-gamma and IgG(2a) production) was only induced in the context of haptens. Heat inactivation of ovalbumin did not diminish the development of a T-H2 immune response. One direct effect of antigen on ECs was the earlier expression of IL-10 mRNA after stimulation with protein allergens (30 minutes) than with haptens (2 hours) in vitro. By using an in vivo approach, sensitization of the skin with trinitrochlorbenzene, but not with ovalbumin, resulted in an early induction of IL-1 beta, IL-12p40, and IFN-gamma mRNA in LNCs,,whereas IL-18 was induced by both.Conclusion: These data indicate that the type of antigen strongly influences the type of immune response by eliciting distinct signals already in the epithelium.