title: Rescue of memory CD8+ T cell reactivity in peptide/TLR9 ligand immunization by codelivery of cytokines or CD40 ligation.
abstract: The capability of cellular immune components to rapidly recall upon challenge in most situations decides the efficacy of a vaccine. Here, we show that immunization of mice with SSIEFARL peptide (immunodominant epitope in glycoprotein B of herpes simplex virus type 1, aa498-505) combined with TLR9 ligand in the absence of helper CD4(+) T cell activation generates a functionally impaired CD8(+) T cell memory response. Codelivery of IL-12, IL-15, or anti-CD40 together with MHC class-I-restricted peptide combined with TLR9 ligand at inception of immunization resulted in generation of memory CD8(+) T cells that were several fold less compromised than immunization with peptide alone. Furthermore, administration of either plasmid DNA encoding IL-15 or anti-CD40 mAb but not rIL-12 during the memory phase restored the reactivity of memory CD8(+) T cells. Moreover, the rescued CD8(+) T cells preserved their cytotoxic capability and were able to clear a recombinant vaccinia virus encoding glycoprotein B of HSV. Our results indicate that good memory CD8(+) T cell response to peptide immunization can be achieved by using costimulatory procedures at the time of priming or recall immunization.
authors.affiliation: Department of Microbiology, M-409 Walter's Life Sciences Building, University of Tennessee, Knoxville, TN 37996-0845, USA.
authors.forename: Felix N
authors.initials: FN
authors.lastname: Toka
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Gieryńska
authors.forename: Susmit
authors.initials: S
authors.lastname: Suvas
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
authors.forename: Barry T
authors.initials: BT
authors.lastname: Rouse
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D018664:Interleukin-12 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000276:immunology*; D051217:Toll-Like Receptor 9; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; D019409:Interleukin-15; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D018664:Interleukin-12