title: Bystander-activated memory CD8 T cells control early pathogen load in an innate-like, NKG2D-dependent manner.
abstract: During an infection the antigen-nonspecific memory CD8 T cell compartment is not simply an inert pool of cells, but becomes activated and cytotoxic. It is unknown how these cells contribute to the clearance of an infection. We measured the strength of T cell receptor (TCR) signals that bystander-activated, cytotoxic CD8 T cells (BA-CTLs) receive in vivo and found evidence of limited TCR signaling. Given this marginal contribution of the TCR, we asked how BA-CTLs identify infected target cells. We show that target cells express NKG2D ligands following bacterial infection and demonstrate that BA-CTLs directly eliminate these target cells in an innate-like, NKG2D-dependent manner. Selective inhibition of BA-CTL-mediated killing led to a significant defect in pathogen clearance. Together, these data suggest an innate role for memory CD8 T cells in the early immune response before the onset of a de novo generated, antigen-specific CD8 T cell response.
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Talyn
authors.initials: T
authors.lastname: Chu
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Tyznik
authors.forename: Sarah
authors.initials: S
authors.lastname: Roepke
authors.forename: Amy M
authors.initials: AM
authors.lastname: Berkley
authors.forename: Amanda
authors.initials: A
authors.lastname: Woodward-Davis
authors.forename: Laura
authors.initials: L
authors.lastname: Pattacini
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bevan
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.forename: Martin
authors.initials: M
authors.lastname: Prlic
mesh_terms: D000818:Animals; D058491:Bacterial Load; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007113:Immunity, Innate; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
chemical_list: C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011948:Receptors, Antigen, T-Cell