Horohov D W, Crim J A, Smith P L, Siegel J P
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
J Immunol. 1988 Dec 15;141(12):4217-23.
The effect of endogenous and exogenous IL-4 on the generation of influenza virus-specific cell-mediated immunity was examined. When added at the onset of the culture, IL-4 augmented both cluster of differentiation (CD)8+ lymphoproliferation and MHC-restricted, influenza virus-specific cytotoxicity. When added 5 or 6 days after initiation of cultures, IL-4 was highly effective at augmenting cytotoxicity, whereas no augmentation of proliferation was observed. This disassociation of the effect of IL-4 on lymphoproliferation and cytotoxicity indicated that IL-4 was providing a late signal in CTL generation. Studied at the level of CTL precursor maturation in microcultures, IL-4 was found not to increase cytotoxicity but to be required, in some cases, for the generation of cytotoxicity. Endogenous IL-4 production was observed and demonstrated to be important because neutralizing antiserum to IL-4 suppressed CTL development. In contrast to the effects of IL-4 when added later to the cultures, pulsing the lymphocytes with IL-4 before, or shortly after, exposure to antigen resulted in suppression of the CTL response. These results indicate that IL-4 has differentiative, proliferative, and suppressive effects on cell-mediated immune responses.
研究了内源性和外源性白细胞介素-4(IL-4)对流感病毒特异性细胞介导免疫产生的影响。在培养开始时添加IL-4,可增强分化簇(CD)8+淋巴细胞增殖以及主要组织相容性复合体(MHC)限制的流感病毒特异性细胞毒性。在培养开始5或6天后添加IL-4,对增强细胞毒性非常有效,而未观察到增殖增强。IL-4对淋巴细胞增殖和细胞毒性作用的这种分离表明,IL-4在细胞毒性T淋巴细胞(CTL)产生过程中提供了一个晚期信号。在微量培养中研究CTL前体成熟水平时发现,IL-4不会增加细胞毒性,但在某些情况下,它是产生细胞毒性所必需的。观察到内源性IL-4的产生,并证明其很重要,因为针对IL-4的中和抗血清会抑制CTL的发育。与在培养后期添加IL-4的作用相反,在淋巴细胞接触抗原之前或之后不久用IL-4刺激淋巴细胞会导致CTL反应受到抑制。这些结果表明,IL-4对细胞介导的免疫反应具有分化、增殖和抑制作用。