title: Memory CD8⁺ T cells can outsource IFN-γ production but not cytolytic killing for antiviral protection.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sanda
authors.initials: S
authors.lastname: Remakus
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rubio
authors.affiliation: Immune Cell Development and Host Defense Program, Research Institute of the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors.forename: Avital
authors.initials: A
authors.lastname: Lev
authors.affiliation: Immune Cell Development and Host Defense Program, Research Institute of the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors.forename: Xueying
authors.initials: X
authors.lastname: Ma
authors.affiliation: Immune Cell Development and Host Defense Program, Research Institute of the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Immune Cell Development and Host Defense Program, Research Institute of the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors.forename: Ren-Huan
authors.initials: RH
authors.lastname: Xu
authors.affiliation: Immune Cell Development and Host Defense Program, Research Institute of the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. Electronic address: luis.sigal@fccc.edu.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Sigal
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004481:Ectromelia virus / Q000276:immunology*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014780:Viruses / Q000276:immunology*
chemical_list: D012900:Smallpox Vaccine; D007371:Interferon-gamma