title: Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination.
abstract: Effector T cells (TEFF) are a barrier to booster vaccination because they can rapidly kill Ag-bearing APCs before memory T cells are engaged. We report in this study that i.v. delivery of rhabdoviral vectors leads to direct infection of follicular B cells in the spleen, where the earliest evidence of secondary T cell responses was observed. This allows booster immunizations to rapidly expand CD8(+) central memory T cells (TCM) during the acute phase of the primary response that is dominated by TEFF Interestingly, although the ablation of B cells before boosting with rhabdoviral vectors diminishes the expansion of memory T cells, B cells do not present Ags directly. Instead, depletion of CD11c(+) dendritic cells abrogates secondary T cell expansion, suggesting that virus-infected follicular B cells may function as an Ag source for local DCs to subsequently capture and present the Ag. Because TCM are located within B cell follicles in the spleen whereas TEFF cannot traffic through follicular regions, Ag production and presentation by follicular APCs represent a unique mechanism to secure engagement of TCM during an ongoing effector response. Our data offer insights into novel strategies for rapid expansion of CD8(+) T cells using prime-boost vaccines by targeting privileged sites for Ag presentation.
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada; and.
authors.forename: Byram W
authors.identifier: 0000-0002-8335-1118
authors.initials: BW
authors.lastname: Bridle
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Omar
authors.initials: O
authors.lastname: Salem
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Liang
authors.identifier: 0000-0002-2512-2384
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Sandeep
authors.identifier: 0000-0003-2836-5813
authors.initials: S
authors.lastname: Koshy
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: Clouthier
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Jonathan
authors.identifier: 0000-0002-8355-7562
authors.initials: J
authors.lastname: Pol
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Stephanie L
authors.identifier: 0000-0002-8545-8322
authors.initials: SL
authors.lastname: Swift
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Dawn M E
authors.initials: DM
authors.lastname: Bowdish
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lichty
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Bramson
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8N 3Z5, Canada wanyong@mcmaster.ca.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D014765:Viral Vaccines