title: Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.
abstract: CD8(+) T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8(+) T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of 'virtual memory' CD8(+) T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of 'virtual memory' CD8(+) T cells in an Eomes-dependent fashion. We further show that the development of 'innate thymic' CD8(+) T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8(+) T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8(+) T cells.
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Valérie
authors.initials: V
authors.lastname: Martinet
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Tonon
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Torres
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Abdulkader
authors.initials: A
authors.lastname: Azouz
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Muriel
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Kohler
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Flamand
authors.affiliation: Department of Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Chai-An
authors.initials: CA
authors.lastname: Mao
authors.affiliation: Department of Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Klein
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.affiliation: WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects / Q000235:genetics*; D007370:Interferon Type I / Q000378:metabolism*; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D060168:Thymocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000941:Antigens; D007370:Interferon Type I; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D007371:Interferon-gamma; D011070:Poly I-C; D053633:Receptor, Interferon alpha-beta; D020825:T-Box Domain Proteins; C491198:Eomes protein, mouse; C508032:Ifnar1 protein, mouse; C494228:Isgf3g protein, mouse