title: Multiple redundant effector mechanisms of CD8+ T cells protect against influenza infection.
abstract: We have previously shown that mice challenged with a lethal dose of A/Puerto Rico/8/34-OVA(I) are protected by injection of 4-8 × 10(6) in vitro-generated Tc1 or Tc17 CD8(+) effectors. Viral load, lung damage, and loss of lung function are all reduced after transfer. Weight loss is reduced and survival increased. We sought in this study to define the mechanism of this protection. CD8(+) effectors exhibit multiple effector activities, perforin-, Fas ligand-, and TRAIL-mediated cytotoxicity, and secretion of multiple cytokines (IL-2, IL-4, IL-5, IL-9, IL-10, IL-17, IL-21, IL-22, IFN-γ, and TNF) and chemokines (CCL3, CCL4, CCL5, CXCL9, and CXCL10). Transfer of CD8(+) effectors into recipients, before infection, elicits enhanced recruitment of host neutrophils, NK cells, macrophages, and B cells. All of these events have the potential to protect against viral infections. Removal of any one, however, of these potential mechanisms was without effect on protection. Even the simultaneous removal of host T cells, host B cells, and host neutrophils combined with the elimination of perforin-mediated lytic mechanisms in the donor cells failed to reduce their ability to protect. We conclude that CD8(+) effector T cells can protect against the lethal effects of viral infection by means of a large number of redundant mechanisms.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Hamada
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bassity
authors.forename: Amanda
authors.initials: A
authors.lastname: Flies
authors.forename: Tara M
authors.initials: TM
authors.lastname: Strutt
authors.forename: Maria de Luz
authors.initials: Mde L
authors.lastname: Garcia-Hernandez
authors.forename: K Kai
authors.initials: KK
authors.lastname: McKinstry
authors.forename: Tie
authors.initials: T
authors.lastname: Zou
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain
authors.forename: Richard W
authors.initials: RW
authors.lastname: Dutton
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D009980:Influenza A virus / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation / Q000821:virology