Immune Cell Development and Host Defense Program, Research Institute of the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA; Department of Microbiology and Immunology, Jefferson Medical College of Thomas Jefferson University, Bluemle Life Sciences Building, 233 South 10(th) Street, Philadelphia, PA 19107, USA.
Immune Cell Development and Host Defense Program, Research Institute of the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Campus de Cantoblanco, 28049 Madrid, Spain.
Cell Host Microbe. 2013 May 15;13(5):546-557. doi: 10.1016/j.chom.2013.04.004.
Immunization with vaccinia virus (VACV), the virus comprising the smallpox vaccine, induces memory CD8(+) T cells that protect from subsequent infections with smallpox in humans or the related ectromelia virus (ECTV) in mice. Memory CD8(+) T cells largely mediate these effects by expanding into secondary effectors that secrete the antiviral cytokine interferon-γ (IFN-γ) and induce cytolysis via releasing factors such as perforin, which permeabilizes target cells. We show that protection from ECTV infection after VACV immunization depends on the initial memory cell frequency and ability of expanded secondary effectors to kill infected targets in a perforin-dependent manner. Although IFN-γ is essential for antiviral protection, it can be produced by either secondary effectors or concomitant primary effector CD8(+) T cells recruited to the response. Thus, during lethal virus challenge, memory CD8(+) T cells are required for cytolytic killing of infected cells, but primary effectors can play important roles by producing IFN-γ.
接种牛痘病毒（VACV），即天花疫苗所包含的病毒，可诱导产生记忆性 CD8(+)T 细胞，从而保护人类免受随后的天花感染或小鼠中相关的腔疹病毒（ECTV）感染。记忆性 CD8(+)T 细胞主要通过扩展为二级效应物来介导这些作用，二级效应物分泌抗病毒细胞因子干扰素-γ（IFN-γ），并通过释放穿孔素等因子诱导细胞溶解，穿孔素使靶细胞通透。我们表明，接种 VACV 后对 ECTV 感染的保护取决于初始记忆细胞频率和扩展后的二级效应物以依赖穿孔素的方式杀死感染靶标的能力。虽然 IFN-γ对于抗病毒保护至关重要，但它可以由二级效应物或募集到反应中的伴随的初始效应性 CD8(+)T 细胞产生。因此，在致死性病毒攻击期间，记忆性 CD8(+)T 细胞对于杀伤感染细胞的细胞溶解是必需的，但是初始效应物可以通过产生 IFN-γ发挥重要作用。
