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.
This article is featured in In This Issue, p.4421
This work was supported by grants from the Canadian Institutes of Health Research and the Ontario Cancer Research Network (to Y.W.).
The online version of this article contains supplemental material.
Abbreviations used in this article:
- recombinant human adenovirus
- dendritic cell
- dopachrome tautomerase
- diphtheria toxin
- diphtheria toxin receptor
- human dopachrome tautomerase
- lymphocytic choriomeningitis virus
- central memory T cell
- effector T cell
- effector memory T cell
- vesicular stomatitis virus
- vaccinia virus
- Received January 19, 2016.
- Accepted April 6, 2016.
- Copyright © 2016 by The American Association of Immunologists, Inc.