title: CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens.
abstract: Self-reactive T cells can escape thymic deletion and therefore some of these potentially autoaggressive T cells need to convert into regulatory T (Treg) cells to help control responses against self. However, it remains unknown how peripheral self-reactive T cells are specifically instructed to become Treg cells. We report that CD5, whose expression is upregulated in T cells by self and tolerizing antigens in the thymus and periphery, governed extrathymic Treg cell development. CD5 modified effector cell-differentiating signals that inhibit Treg cell induction. Treg cell conversion of Cd5(-/-) and CD5(lo) T cells was inhibited by even small amounts of interleukin-4 (IL-4), IL-6, and interferon-γ (IFN-γ) produced by bystander lymphocytes, while CD5(hi) T cells resisted this inhibition of Treg cell induction. Our findings further revealed that CD5 promoted Treg cell induction by blocking mechanistic target of rapamycin (mTOR) activation. Therefore CD5 instructs extrathymic Treg cell development in response to self and tolerizing antigens.
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Henderson
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Adeleye
authors.initials: A
authors.lastname: Opejin
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jones
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Gross
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA. Electronic address: dhawiger@slu.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hawiger
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D024201:Bystander Effect / Q000276:immunology; D018956:CD5 Antigens / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D061166:Peripheral Tolerance; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D001324:Autoantigens; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D015850:Interleukin-6; D015847:Interleukin-4; D007371:Interferon-gamma; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases