Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Th1 phenotype
Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Th1 phenotype
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DOI：
10.1182/blood.v90.5.1920
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发表时间：
1997-09-01
期刊：
影响因子：
20.3
通讯作者：
Kapsenberg, ML
中科院分区：
文献类型：
--
作者：
Hilkens, CMU;Kalinski, P;Kapsenberg, ML
树突状细胞(DC)是唯一能有效激活初始Th细胞的APC，是特异性初级免疫应答的重要启动者。DC具有产生白介素12(IL-12)的能力，IL-12是一种在Th1介导的细胞免疫反应中起关键作用的细胞因子。本研究的重点是人类DC产生生物活性IL-12p70的条件，从而引导幼稚T辅助细胞(Th)向Th1表型发展。细菌或细菌化合物如金黄色葡萄球菌Cowan菌株I(SAG)或脂多糖(LPS)可诱导DC产生大量IL-12，干扰素-伽马可进一步上调IL-12水平，而通过CD40连接诱导IL-12产生则需要干扰素-伽马作为必需的补充信号。此外，激活的初始Th细胞是产生IL-12的不良诱导者，除非存在外源性LFN-γ，而激活的记忆Th细胞是产生IL-12的有效诱导者，不需要外源性干扰素-γ。接下来，我们检测了不同条件下DC诱导的成熟Th细胞的细胞因子谱。DC促进原始Th细胞发育为记忆性Th0细胞，从而产生1型细胞因子干扰素-伽马和2型细胞因子IL-4。相反，在SAG激活后，DC通过释放IL-12有效地指导Th1细胞的发育，这是一个APC非依赖的Bh细胞成熟模型，使用重组IL-12或SAG激活的DC的上清并中和抗IL-12抗体，证实DC来源的IL-12是主要的Th1扭曲因子。综上所述，这些数据表明，DC和初始Th细胞在启动特异性免疫反应过程中的接触并不能有效地诱导IL-12的产生，因此，需要外源IL-12诱导因子来促进Th1介导的原始细胞免疫反应。(C)1997年由美国血液病学会主办。
Dendritic cells [DC) are important initiators of specific primary immune responses because they are the only APC that can efficiently activate naive Th cells. DC have the capacity to produce interleukin-12 (IL-12), a cytokine that plays a pivotal role in the development of Th1-mediated cellular immune responses. The present study focuses on the conditions under which human DC produce bioactive IL-12 p70 and, consequently, direct the development of naive T helper (Th) cells toward the Th1 phenotype. Bacteria or bacterial compounds such as Staphylococcus aureus Cowan strain I (SAG) or lipopolysaccharide (LPS) induced substantial IL-12 levels in DC, which could be further upregulated by interferon-gamma (IFN-gamma), whereas induction of IL-12 production via CD40 ligation required IFN-gamma as an obligatory, complementary signal. Also, activated naive Th cells were poor inducers of IL-12 production, unless exogenous lFN-gamma was present, whereas activated memory Th cells were effective inducers of IL-12 production and did not require exogenous IFN-gamma. Next, the cytokine profiles of matured Th cells that were primed by DC under different conditions were examined. DC promoted the development of naive Th cells into memory Th0 cells that produced both the type 1 cytokine IFN-gamma and the type 2 cytokine IL-4. In contrast, after activation with SAG, DC efficiently directed the development of Th1 cells through the release of IL-12, An APC-independent Bh cell maturation model, using either recombinant IL-12 or supernatants of SAG-activated DC and neutralizing anti-IL-12 antibodies, confirmed that DC-derived IL-12 was the major Th1 skewing factor. Together, these data indicate that the contact between DC and naive Th cells during the initiation of specific immune responses does not result in the efficient induction of IL-12 production and that, consequently, exogenous IL-12-inducing factors are required to promote primary Th1-mediated cellular immune responses. (C) 1997 by The American Society of Hematology.