title: CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection.
abstract: The co-stimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming, we generated a strain of mice where CD28 is removed from CD4(+) T cells after priming. We show that continued CD28 expression is important for effector CD4(+) T cells following infection; maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. Persistent CD28 is also required for clearance of the bacterium Citrobacter rodentium from the gastrointestinal tract. Together, this study demonstrates that CD28 persistence is required for helper T cell polarization in response to infection, describing a novel function for CD28 that is distinct from its role in T cell priming.
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Linterman
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Alice E
authors.initials: AE
authors.lastname: Denton
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Devina P
authors.initials: DP
authors.lastname: Divekar
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Ilona
authors.initials: I
authors.lastname: Zvetkova
authors.affiliation: Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
authors.forename: Leanne
authors.initials: L
authors.lastname: Kane
authors.affiliation: Babraham Research Campus, Babraham Institute, Cambridge, United Kingdom.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Babraham Research Campus, Babraham Institute, Cambridge, United Kingdom.
authors.forename: Marc
authors.identifier: http://orcid.org/0000-0002-1478-9562
authors.initials: M
authors.lastname: Veldhoen
authors.affiliation: Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.affiliation: Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Marion
authors.initials: M
authors.lastname: Espéli
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D044082:Citrobacter rodentium / Q000502:physiology*; D045142:Cross-Priming / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007109:Immunity; D007111:Immunity, Cellular; D009980:Influenza A virus / Q000502:physiology; D019426:Integrases / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology; D053262:Receptors, OX40 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008024:Ligands; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; C045073:Cre recombinase; D019426:Integrases
keywords: CD28; helper T cells; immunology; infection; mouse