Langenkamp A, Messi M, Lanzavecchia A, Sallusto F
Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
Nat Immunol. 2000 Oct;1(4):311-6. doi: 10.1038/79758.
To prime immune responses, dendritic cells (DCs) need to be activated to acquire T cell stimulatory capacity. Although some stimuli trigger interleukin 12 (IL-12) production that leads to T helper cell type I (TH1) polarization, others fail to do so and favor TH2 polarization. We show that after activation by lipopolysaccharide, DCs produced IL-12 only transiently and became refractory to further stimulation. The exhaustion of cytokine production impacted the T cell polarizing process. Soon after stimulation DCs primed strong TH1 responses, whereas at later time points the same cells preferentially primed TH2 and nonpolarized T cells. These findings indicate that during an immune response, T cell priming conditions may change in the lymph nodes, suggesting another mechanism for the regulation of effector and memory T cells.
为启动免疫反应,树突状细胞(DCs)需要被激活以获得T细胞刺激能力。尽管一些刺激可触发白细胞介素12(IL-12)的产生,进而导致I型辅助性T细胞(TH1)极化,但其他刺激则无法做到这一点,反而有利于TH2极化。我们发现,脂多糖激活后的DCs仅短暂产生IL-12,并对进一步刺激产生耐受。细胞因子产生的耗竭影响了T细胞极化过程。刺激后不久,DCs启动强烈的TH1反应,而在随后的时间点,相同的细胞优先启动TH2和非极化T细胞。这些发现表明,在免疫反应过程中,淋巴结中的T细胞启动条件可能会发生变化,这提示了另一种调节效应性T细胞和记忆性T细胞的机制。