title: FliC-specific CD4+ T cell responses are restricted by bacterial regulation of antigen expression.
abstract: Salmonella typhimurium, a facultatively intracellular pathogen, regulates expression of virulence factors in response to distinct environments encountered during the course of infection. We tested the hypothesis that the transition from extra- to intracellular environments during Salmonella infection triggers changes in Ag expression that impose both temporal and spatial limitations on the host T cell response. CD4(+) T cells recovered from Salmonella immune mice were propagated in vitro using Ag derived from bacteria grown in conditions designed to emulate extra- or intracellular environments in vivo. Extracellular phase bacteria supported a dominant T cell response to the flagellar subunit protein FliC, whereas intracellular phase bacteria were unable to support expansion of FliC-specific T cells from populations known to contain T cells with reactivity to this Ag. This result was attributed to bacterial regulation of FliC expression: transcription and protein levels were repressed in bacteria growing in the spleens of infected mice. Furthermore, Salmonella-infected splenocytes taken directly ex vivo stimulated FliC-specific T cell clones only when intracellular FliC expression was artificially up-regulated. Although it has been suggested that a microanatomical separation of immune T cells and infected APC exists in vivo, we demonstrate that intracellular Salmonella can repress FliC expression below the T cell activation threshold. This potentially provides a mechanism for intracellular Salmonella at systemic sites to avoid detection by Ag-specific T cells primed at intestinal sites early in infection.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cummings
authors.forename: Sara L Rassoulian
authors.initials: SL
authors.lastname: Barrett
authors.forename: W David
authors.initials: WD
authors.lastname: Wilkerson
authors.forename: Ivana
authors.initials: I
authors.lastname: Fellnerova
authors.forename: Brad T
authors.initials: BT
authors.lastname: Cookson
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D005110:Extracellular Space / Q000276:immunology / Q000382:microbiology; D005260:Female; D005408:Flagellin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology*; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D005408:Flagellin