Privileged antigen presentation in splenic B cell follicles maximizes T cell responses in prime-boost vaccination

BW Bridle, A Nguyen, O Salem, L Zhang… - The Journal of …, 2016 - journals.aai.org
BW Bridle, A Nguyen, O Salem, L Zhang, S Koshy, D Clouthier, L Chen, J Pol, SL Swift…
The Journal of immunology, 2016journals.aai.org
Abstract Effector T cells (T EFF) 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 iv
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 (T CM) during the
acute phase of the primary response that is dominated by T EFF. Interestingly, although the …
Abstract
Effector T cells (T EFF) 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 iv 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 (T CM) during the acute phase of the primary response that is dominated by T EFF. 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 T CM are located within B cell follicles in the spleen whereas T EFF cannot traffic through follicular regions, Ag production and presentation by follicular APCs represent a unique mechanism to secure engagement of T CM 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.
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