Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination

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 o...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2016-06, Vol.196 (11), p.4587-4595
Main Authors: Bridle, Byram W, Nguyen, Andrew, Salem, Omar, Zhang, Liang, Koshy, Sandeep, Clouthier, Derek, Chen, Lan, Pol, Jonathan, Swift, Stephanie L, Bowdish, Dawn M E, Lichty, Brian D, Bramson, Jonathan L, Wan, Yonghong
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation - immunology
B-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Dendritic Cells, Follicular - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Spleen - cytology
Spleen - immunology
Vesicular stomatitis Indiana virus - immunology
Viral Vaccines - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1600106