https://orcid.org/0000-0002-8335-1118
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Byram W Bridle, Andrew Nguyen, Omar Salem, Liang Zhang, Sandeep Koshy, Derek Clouthier, Lan Chen, Jonathan Pol, Stephanie L Swift, Dawn M E Bowdish, Brian D Lichty, Jonathan L Bramson, Yonghong Wan, Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination, The Journal of Immunology, Volume 196, Issue 11, June 2016, Pages 4587–4595, https://doi.org/10.4049/jimmunol.1600106
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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.
