title: Cutting Edge: CD28 controls dominant regulatory T cell activity during active immunization.
abstract: Ligation of CD28 during Ag recognition plays an important role in the generation of effective T cell responses. However, its peripheral control of regulatory T cell function remains obscure. In this study, we show that naive wild-type or CD28(-/-) CD4(+)CD25(-) T cells exposed to peptide in vivo develop regulatory activity that suppresses the response of adoptively transferred naive T cells to a subsequent immunogenic challenge. We find that although CD28 is engaged during the initial peptide-priming event and is essential to sustain T cell survival, it is not sufficient to prevent the dominance of regulatory T cell function. Immunization with adjuvant abrogates regulatory dominance, reducing overall Foxp3 expression in a CD28-dependent manner. We conclude that CD28 licenses active immunization by regulating Ag-induced immunoregulation.
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Clay
authors.initials: C
authors.lastname: Lyddane
authors.forename: Beata U
authors.initials: BU
authors.lastname: Gajewska
authors.forename: Elmer
authors.initials: E
authors.lastname: Santos
authors.forename: Philip D
authors.initials: PD
authors.lastname: King
authors.forename: Glaucia C
authors.initials: GC
authors.lastname: Furtado
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
chemical_list: D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2