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Remakus S , Rubio D , Lev A , Ma X , Fang M , Xu RH , Sigal LJ
Memory CD8(+) T Cells Can Outsource IFN-gamma Production but Not Cytolytic Killing for Antiviral Protection
Cell Host Microbe. 2013 May 15;13(5) :546-57
PMID: 23684306   
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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-gamma (IFN-gamma) 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-gamma 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-gamma.
Remakus, Sanda Rubio, Daniel Lev, Avital Ma, Xueying Fang, Min Xu, Ren-Huan Sigal, Luis J P30 CA006927/CA/NCI NIH HHS/United States R01 AI048849/AI/NIAID NIH HHS/United States R01 AI065544/AI/NIAID NIH HHS/United States T32 CA009035/CA/NCI NIH HHS/United States U19 AI083008/AI/NIAID NIH HHS/United States United States Cell host & microbe Nihms471005 Cell Host Microbe. 2013 May 15;13(5):546-57. doi: 10.1016/j.chom.2013.04.004.