title: Persistent loss of IL-27 responsiveness in CD8+ memory T cells abrogates IL-10 expression in a recall response.
abstract: CD8+ T cells are central to the eradication of intracellular pathogens, but they can also act to limit inflammation and immunopathology. During primary respiratory viral infection CD8+ effector T cells release the immunosuppressive cytokine IL-10, which is essential for host survival. Here we report that CD8+ T-cell-derived IL-10 is absent in a recall response. We show in mice that the lack of IL-10 is due to a persistent loss of IL-27 responsiveness in CD8+ memory T cells, caused by down-regulation of the common cytokine receptor, glycoprotein 130. CD8+ memory T cells secreted less IL-10 when activated in the presence of IL-27 than did naïve controls, and retroviral expression of glycoprotein 130 restored IL-10 and reduced IFN-γ production upon restimulation. We demonstrate that human CD8+ memory cells are also characterized by impaired IL-27 responsiveness. Our data suggest that CD8+ T-cell activation involves a persistent loss of specific cytokine receptors that determines the functional potential of these cells during rechallenge infection.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA. gperona@mail.ubc.ca
authors.forename: Georgia
authors.initials: G
authors.lastname: Perona-Wright
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Kohlmeier
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bassity
authors.forename: Tori C
authors.initials: TC
authors.lastname: Freitas
authors.forename: Katja
authors.initials: K
authors.lastname: Mohrs
authors.forename: Tres
authors.initials: T
authors.lastname: Cookenham
authors.forename: Haozhong
authors.initials: H
authors.lastname: Situ
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.forename: Markus
authors.initials: M
authors.lastname: Mohrs
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D016753:Interleukin-10 / Q000276:immunology*; D020381:Interleukin-17 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D012141:Respiratory Tract Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D020381:Interleukin-17; D016753:Interleukin-10; D050822:Cytokine Receptor gp130