title: Autophagy is essential for effector CD8(+) T cell survival and memory formation.
abstract: The importance of autophagy in the generation of memory CD8(+) T cells in vivo is not well defined. We report here that autophagy was dynamically regulated in virus-specific CD8(+) T cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the current paradigm, autophagy decreased in activated proliferating effector CD8(+) T cells and was then upregulated when the cells stopped dividing just before the contraction phase. Consistent with those findings, deletion of the gene encoding either of the autophagy-related molecules Atg5 or Atg7 had little to no effect on the proliferation and function of effector cells, but these autophagy-deficient effector cells had survival defects that resulted in compromised formation of memory T cells. Our studies define when autophagy is needed during effector and memory differentiation and warrant reexamination of the relationship between T cell activation and autophagy.
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Araki
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Shuzhao
authors.initials: S
authors.lastname: Li
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Han
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Lilin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Tan
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Bogumila T
authors.initials: BT
authors.lastname: Konieczny
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Monique W
authors.initials: MW
authors.lastname: Bruinsma
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Pearce
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D002853:Chromatography, Liquid; D005434:Flow Cytometry; D015151:Immunoblotting; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D013058:Mass Spectrometry; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D014161:Transduction, Genetic