title: A role for apoptosis-inducing factor in T cell development.
abstract: Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues. We report that aif-hypomorphic harlequin (Hq) mice show thymic hypocellularity and a cell-autonomous thymocyte developmental block associated with apoptosis at the β-selection stage, independent of T cell receptor β recombination. No abnormalities are observed in the B cell lineage. Transgenes encoding wild-type or DNA-binding-deficient mutant Aif rectify the thymic defect, but a transgene encoding oxidoreductase activity-deficient mutant Aif does not. The Hq thymic block is reversed in vivo by antioxidant treatment, and Hq T but not B lineage cells show enhanced oxidative stress. Thus, Aif, a ubiquitous protein, serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic β-selection.
authors.affiliation: National Institute of Immunology, New Delhi 110067, India.
authors.forename: Hridesh
authors.initials: H
authors.lastname: Banerjee
authors.forename: Abhishek
authors.initials: A
authors.lastname: Das
authors.forename: Smita
authors.initials: S
authors.lastname: Srivastava
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Mattoo
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Thyagarajan
authors.forename: Jasneet Kaur
authors.initials: JK
authors.lastname: Khalsa
authors.forename: Shalini
authors.initials: S
authors.lastname: Tanwar
authors.forename: Deepika Sharma
authors.initials: DS
authors.lastname: Das
authors.forename: Subeer S
authors.initials: SS
authors.lastname: Majumdar
authors.forename: Anna
authors.initials: A
authors.lastname: George
authors.forename: Vineeta
authors.initials: V
authors.lastname: Bal
authors.forename: Jeannine M
authors.initials: JM
authors.lastname: Durdik
authors.forename: Satyajit
authors.initials: S
authors.lastname: Rath
mesh_terms: D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000502:physiology*; D016923:Cell Death; D019070:Cell Lineage; D004247:DNA / Q000378:metabolism; D005260:Female; D019674:Genes, T-Cell Receptor beta; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000502:physiology*; D060168:Thymocytes / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000254:growth & development / Q000473:pathology
chemical_list: D051033:Apoptosis Inducing Factor; C494830:AIFM1 protein, mouse; D017382:Reactive Oxygen Species; D004247:DNA