title: Stimulation of enhanced CD8 T cell responses following immunization with a hyper-antigen secreting intracytosolic bacterial pathogen.
abstract: The intracytosolic niche for replication of Listeria monocytogenes (Lm) facilitates delivery of bacteria-derived Ags into the MHC class I pathway for subsequent stimulation of CD8 effector T cells. Using Lm strains that are equivalent for in vivo virulence yet express marked differences in the level of secretion of a protective target Ag, we have evaluated how these specific differences in secretion levels influences the magnitude and effector function of Ag-specific CD8 T cell responses following Lm injection. Immunization with low doses of a hyperantigen-secreting Lm strain stimulated enhanced target-Ag specific CD8 T cell responses compared with the magnitude stimulated following immunization with the same dose of wild-type Lm. The enhanced determinant-specific response was also evident by in vivo CTL activity, increased numbers of memory cells 4 wk following immunization, and enhanced antilisterial protection following a challenge infection. Initiation of antibiotic treatment 24 h following infection with wild-type Lm markedly reduced the magnitude of the effector CD8 T cell response. In contrast, antibiotic treatment initiated 24 h following immunization with the hyperantigen secreting strain of Lm did not impact the frequency of the target-Ag specific CD8 T cells. Thus, immunization with a low dose of a hyperantigen secreting Lm strain, followed by antibiotic treatment to limit the extent of the infection, may represent a safe strategy for the stimulation of enhanced effector CD8 T cell responses to specific Ag by a rLm vaccine.
authors.affiliation: Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Smithey
authors.forename: Suzanne
authors.initials: S
authors.lastname: Brandt
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Freitag
authors.forename: Darren E
authors.initials: DE
authors.lastname: Higgins
authors.forename: H G Archie
authors.initials: HG
authors.lastname: Bouwer
mesh_terms: D000667:Ampicillin / Q000008:administration & dosage; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D002460:Cell Line; D003600:Cytosol / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015854:Up-Regulation / Q000276:immunology; D014774:Virulence / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D000667:Ampicillin; C038705:hlyA protein, Listeria monocytogenes