title: Production of IL-10 by CD4(+) regulatory T cells during the resolution of infection promotes the maturation of memory CD8(+) T cells.
abstract: Memory CD8(+) T cells are critical for host defense upon reexposure to intracellular pathogens. We found that interleukin 10 (IL-10) derived from CD4(+) regulatory T cells (Treg cells) was necessary for the maturation of memory CD8(+) T cells following acute infection with lymphocytic choriomeningitis virus (LCMV). Treg cell-derived IL-10 was most important during the resolution phase, calming inflammation and the activation state of dendritic cells. Adoptive transfer of IL-10-sufficient Treg cells during the resolution phase 'restored' the maturation of memory CD8(+) T cells in IL-10-deficient mice. Our data indicate that Treg cell-derived IL-10 is needed to insulate CD8(+) T cells from inflammatory signals, and reveal that the resolution phase of infection is a critical period that influences the quality and function of developing memory CD8(+) T cells.
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Laidlaw
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cui
authors.affiliation: 1] Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Amezquita
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Gray
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Tianxia
authors.initials: T
authors.lastname: Guan
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Yisi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: 1] Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: 1] Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA. [2] Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA. [3] Interdepartmental Program in Computational Biology and Bioinformatics, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.affiliation: 1] Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA. [2] Department of Internal Medicine (Rheumatology), Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Craft
authors.affiliation: 1] Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10