title: FoxO3 is a negative regulator of primary CD8+ T-cell expansion but not of memory formation.
abstract: The generation of CD8(+) T cells by vaccination represents an important goal for protective immunity to infectious pathogens. It is thus of utmost importance to understand the mechanisms involved in the generation of optimal CD8(+) T-cell responses. The forkhead box O (FoxO) family of transcription factors has a crucial role in cellular responses to environmental change. Among them, FoxO3 is critically involved in the regulation of cellular proliferation, apoptosis, metabolism and stress resistance to withdrawal of nutrients or cytokine growth factors. Since the role of FoxO3 has been poorly studied in the immune system, here we have evaluated its involvement in the CD8(+) T-cell response. We observe that CD8(+) T cells deficient for FoxO3 undergo a significantly greater primary expansion than their wild-type (WT) counterparts in response to both infectious (vaccinia virus) or non-infectious (non-replicating cellular vaccine) immunogens, resulting in a larger cohort of cells following contraction. These survivors, however, do not undergo a greater secondary response than WT. Taken together, our data show that FoxO3 is a negative regulator of the CD8(+) T-cell response, specifically during the primary expansion.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Togher
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Larange
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Feau
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse