title: RETRACTED: T cell metabolism. The protein LEM promotes CD8⁺ T cell immunity through effects on mitochondrial respiration.
abstract: Protective CD8(+) T cell-mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8(+) T cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. Generation of LEM-deficient mice confirmed these results. Through interaction with CR6 interacting factor (CRIF1), LEM controlled the levels of oxidative phosphorylation (OXPHOS) complexes and respiration, resulting in the production of pro-proliferative mitochondrial reactive oxygen species (mROS). LEM provides a link between immune activation and the expansion of protective CD8(+) T cells driven by OXPHOS and represents a pathway for the restoration of long-term protective immunity based on metabolically modified cytotoxic CD8(+) T cells.
authors.affiliation: Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Isobel
authors.initials: I
authors.lastname: Okoye
authors.affiliation: Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule Zurich (ETHZ), Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pallmer
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule Zurich (ETHZ), Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Richter
authors.affiliation: Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Takahuru
authors.initials: T
authors.lastname: Ichimura
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Haas
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule Zurich (ETHZ), Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Josh
authors.initials: J
authors.lastname: Crouse
authors.affiliation: Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Onjee
authors.initials: O
authors.lastname: Choi
authors.affiliation: Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Dean
authors.initials: D
authors.lastname: Heathcote
authors.affiliation: Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Lovo
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Claudio
authors.initials: C
authors.lastname: Mauro
authors.affiliation: Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Abdi
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule Zurich (ETHZ), Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
authors.affiliation: Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rutschmann
authors.affiliation: Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK. Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02215, USA. p.ashton-rickardt@imperial.ac.uk.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Ashton-Rickardt
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D019069:Cell Respiration; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C527307:Crif1 protein, mouse; C000599092:LEM protein, mouse; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species