Berg Rance E, Crossley Emily, Murray Sean, Forman James
University of Texas Southwestern Medical Center, Center for Immunology, 6000 Harry Hines Blvd., NA2.200, Dallas, TX 75390-9093, USA.
J Exp Med. 2003 Nov 17;198(10):1583-93. doi: 10.1084/jem.20031051.
Interferon (IFN)-gamma plays an important role in the innate immune response against intracellular bacterial pathogens. It is commonly thought that natural killer cells are the primary source of this cytokine that is involved in activating antibacterial effects in infected cells and polarizing CD4+ T cells toward the Th1 subset. However, here we show that both effector and memory CD8+ T cells have the potential to secrete IFN-gamma in response to interleukin (IL)-12 and IL-18 in the absence of cognate antigen. We demonstrate that memory CD8+ T cells specific for the ovalbumin protein secrete IFN-gamma rapidly after infection with wild-type Listeria monocytogenes (LM). Furthermore, small numbers of ovalbumin-specific, memory CD8+ T cells can reduce spleen and liver bacterial counts in IFN-gamma-deficient mice 3 d after LM infection. Up-regulation of the receptors for IL-12 and IL-18 provides a mechanism for the ability of memory CD8+ T cells to respond in this antigen nonspecific manner. Thus, CD8+ T cells play an important role in the innate immune response against intracellular pathogens by rapidly secreting IFN-gamma in response to IL-12 and IL-18.
干扰素（IFN）-γ在针对细胞内细菌病原体的固有免疫反应中发挥重要作用。通常认为自然杀伤细胞是这种细胞因子的主要来源，它参与激活受感染细胞中的抗菌作用，并使CD4+T细胞向Th1亚群极化。然而，我们在此表明，效应性和记忆性CD8+T细胞在缺乏同源抗原的情况下，有潜力响应白细胞介素（IL）-12和IL-18而分泌IFN-γ。我们证明，针对卵清蛋白的记忆性CD8+T细胞在感染野生型单核细胞增生李斯特菌（LM）后迅速分泌IFN-γ。此外，少量卵清蛋白特异性记忆性CD8+T细胞可在LM感染3天后降低IFN-γ缺陷小鼠脾脏和肝脏中的细菌数量。IL-12和IL-18受体的上调为记忆性CD8+T细胞以这种抗原非特异性方式做出反应的能力提供了一种机制。因此，CD8+T细胞通过响应IL-12和IL-18迅速分泌IFN-γ，在针对细胞内病原体的固有免疫反应中发挥重要作用。
