Saito S, Dorf M E, Watanabe N, Tadakuma T
Division of Morphology, Jikei University School of Medicine, Tokyo, Japan.
Cell Immunol. 1994 Jan;153(1):1-8. doi: 10.1006/cimm.1994.1001.
The transition of lymphokine production from IL-2 to IL-4 was investigated with antigen-primed lymph node cells (LNC) by observing cytokine release following sequential cycles of antigen exposure in vitro. LNC from mice infected with Nippostrongylus brasiliensis (Nb), Trichinella spiralis, or primed with giant ragweed pollen demonstrated a pattern of dominant IL-2 production at 24 hr; however, there was a switch to predominantly IL-4 production within 72 hr following the first cycle of in vitro antigenic stimulation. In addition, repeated antigenic stimulation with these antigens shifted the pattern to IL-4 production. In contrast, only IL-2 production was observed after a single cycle of in vitro antigenic challenge with haptens (e.g., NP-O-succinimide or trimethylammonium hapten) or the naive allogenic spleen cells. Thereafter, the lymphokine production pattern gradually changed from IL-2 alone to mixtures of IL-2 and IL-4, and finally to predominant IL-4 secretion. In contrast, following priming with purified protein derivatives (PPD), it was difficult to detect IL-4 release even after nine successive weekly stimulations. However, activation of PPD-primed cells with anti-CD3 antibody resulted in IL-4 secretion. Furthermore, Nb-primed T cells, which produced IL-4 alone after repeated antigenic stimulation, produced IL-2 when stimulated in the presence of cycloheximide. These results suggest that (1) immune populations regulate cytokine production, (2) the IL-2/IL-4 profile is dependent on the type and duration of antigenic stimulation, and (3) production or accumulation of cycloheximide-sensitive proteins is critical for the switch from IL-2 to IL-4 secretion.
通过观察体外连续抗原暴露周期后的细胞因子释放情况，利用抗原致敏的淋巴结细胞（LNC）研究了淋巴因子产生从白细胞介素-2（IL-2）向白细胞介素-4（IL-4）的转变。感染巴西日圆线虫（Nb）、旋毛虫的小鼠或用豚草花粉致敏的小鼠的LNC在24小时时表现出以IL-2产生为主的模式；然而，在体外抗原刺激的第一个周期后的72小时内，转变为主要产生IL-4。此外，用这些抗原反复进行抗原刺激会使模式转变为产生IL-4。相比之下，在用半抗原（如NP-O-琥珀酰亚胺或三甲基铵半抗原）或未致敏的同种异体脾细胞进行单个体外抗原攻击周期后，仅观察到IL-2的产生。此后，淋巴因子产生模式逐渐从仅产生IL-2转变为IL-2和IL-4的混合物，最终转变为主要分泌IL-4。相比之下，在用纯化蛋白衍生物（PPD）致敏后，即使经过连续九周每周一次的刺激，也很难检测到IL-4的释放。然而，用抗CD3抗体激活PPD致敏的细胞会导致IL-4分泌。此外，反复抗原刺激后单独产生IL-4的Nb致敏T细胞在存在放线菌酮的情况下受到刺激时会产生IL-2。这些结果表明：（1）免疫群体调节细胞因子的产生；（2）IL-2/IL-4谱取决于抗原刺激的类型和持续时间；（3）放线菌酮敏感蛋白的产生或积累对于从分泌IL-2向分泌IL-4的转变至关重要。
