DeKruyff R H, Fang Y, Umetsu D T
Department of Pediatrics, Stanford University, CA 94305.
J Immunol. 1992 Dec 1;149(11):3468-76.
The development of IL-4 synthesis is a critical step in the regulation of immune responses. Our studies focused on the production of IL-4 by CD4+ T cells taken from mice primed with the Ag keyhole limpet hemocyanin (KLH). In vitro stimulation of such CD4+ T cells with KLH resulted in little or no IL-4 production in the first 24 h of stimulation, indicating that little IL-4 synthesis persists in vivo after immunization. However, IL-4 was generated later at 24 to 96 h of in vitro stimulation, indicating that the potential to produce IL-4 was retained by the KLH-primed CD4+ T cells, but that in vitro maturation of the T cells was required before initiation of IL-4 production. The amount of IL-4 produced in vitro by KLH-primed T cells from BALB/c mice was influenced by several factors. First, stimulation of KLH-primed CD4+ T cells with higher in vitro concentrations of KLH resulted in more IL-4 synthesis, but this was accompanied by more IFN-gamma as well. Second, primed CD4+ T cells from lymph nodes (axillary and popliteal) produced significantly more IL-4 than primed splenic T cells. Third, when primed B cells were utilized to present low concentrations of KLH to the T cells, IL-4 but not IFN-gamma was produced. In contrast, use of splenic adherent cells resulted in IFN-gamma but not IL-4 synthesis. These restricted patterns of lymphokine synthesis, however, were observed only with low concentrations of KLH. Fourth, the amount of IL-4 produced and its regulation by the presence of IFN-gamma differed among mouse strains, in that BALB/c T cells produced much more IL-4 than H-2 identical DBA/2 T cells. Our results characterizing the APC and Ag dose requirements for IL-4 synthesis in KLH-primed T cells from different strains of mice are consistent with previous observations that distinct strains of mice differ in the type of immune response generated against different pathogens, and with the concept that low Ag concentrations preferentially result in high levels of IgE synthesis, which is absolutely dependent on IL-4 production.
白细胞介素-4（IL-4）合成的发展是免疫反应调节中的关键步骤。我们的研究聚焦于用抗原钥孔戚血蓝蛋白（KLH）免疫的小鼠体内分离出的CD4⁺ T细胞产生IL-4的情况。体外使用KLH刺激此类CD4⁺ T细胞，在刺激的最初24小时内几乎没有或根本没有IL-4产生，这表明免疫后体内持续存在的IL-4合成很少。然而，在体外刺激24至96小时后产生了IL-4，这表明用KLH免疫的CD4⁺ T细胞保留了产生IL-4的潜力，但在开始产生IL-4之前需要T细胞进行体外成熟。来自BALB/c小鼠的用KLH免疫的T细胞在体外产生的IL-4量受几个因素影响。首先，用体外更高浓度的KLH刺激用KLH免疫的CD4⁺ T细胞会导致更多的IL-4合成，但同时也会产生更多的干扰素-γ（IFN-γ）。其次，来自淋巴结（腋窝和腘窝）的免疫CD4⁺ T细胞产生的IL-4明显多于免疫的脾T细胞。第三，当用免疫的B细胞向T细胞呈递低浓度的KLH时，会产生IL-4而不产生IFN-γ。相反，使用脾黏附细胞会导致产生IFN-γ而不产生IL-4合成。然而，这些细胞因子合成的受限模式仅在低浓度的KLH下观察到。第四，不同小鼠品系中产生的IL-4量及其受IFN-γ存在的调节情况不同，因为BALB/c T细胞产生的IL-4比H-2相同的DBA/2 T细胞多得多。我们对来自不同品系小鼠的用KLH免疫的T细胞中IL-4合成的抗原呈递细胞（APC）和抗原剂量要求进行表征的结果，与先前的观察结果一致，即不同品系的小鼠针对不同病原体产生的免疫反应类型不同，也与低抗原浓度优先导致高水平IgE合成的概念一致，而IgE合成绝对依赖于IL-4的产生。
