Bhardwaj N, Seder R A, Reddy A, Feldman M V
Rockefeller University, New York 10021, USA.
J Clin Invest. 1996 Aug 1;98(3):715-22. doi: 10.1172/JCI118843.
CD8+ cytolytic T lymphocytes (CTLs) are important mediators for resistance to infections and malignant diseases. IL-12 enhances proliferative and cytolytic responses by killer cells, but its function in the generation of human antiviral CD8+ T cell responses has not been defined. We therefore evaluated the role of IL-12 in the generation of CTLs to influenza-infected dendritic cells. IL-12 was not detectable in supernatants of infected-dendritic cells, or during CTL generation. Furthermore, anti-IL-12 antibody did not block CTL generation. However, exogenous IL-12 (30-300 pg/ml) enhanced CD8+ T cell proliferative and cytolytic responses. The effect was greatest in individuals with weak reactivity to influenza virus or at antigen-presenting cell (APC):T cell ratios of 1:100 or less. IL-12 augmented interferon-gamma production during CTL generation. The CTL enhancing effects of the cytokine, however, could not be blocked by neutralizing anti-interferon-gamma antibody. Together with IL-12, antigen-pulsed dendritic cells may be a useful approach for boosting CTL responses against infectious agents and malignancies.
CD8 + 细胞毒性T淋巴细胞（CTL）是抵抗感染和恶性疾病的重要介质。白细胞介素-12（IL-12）可增强杀伤细胞的增殖和细胞溶解反应，但其在人类抗病毒CD8 + T细胞反应产生中的作用尚未明确。因此，我们评估了IL-12在针对流感感染的树突状细胞产生CTL中的作用。在感染的树突状细胞上清液中或CTL产生过程中均未检测到IL-12。此外，抗IL-12抗体并未阻断CTL的产生。然而，外源性IL-12（30 - 300 pg/ml）增强了CD8 + T细胞的增殖和细胞溶解反应。在对流感病毒反应较弱的个体中，或在抗原呈递细胞（APC）与T细胞比例为1:100或更低时，这种作用最为明显。IL-12在CTL产生过程中增加了γ干扰素的产生。然而，细胞因子对CTL的增强作用不能被中和性抗γ干扰素抗体阻断。与IL-12一起，抗原脉冲树突状细胞可能是增强针对感染因子和恶性肿瘤的CTL反应的一种有用方法。
