| Autor: |
Wüthrich, Marcel, Ersland, Karen, Pick-Jacobs, John C., Gern, Benjamin H., Frye, Christopher A., Sullivan, Thomas D., Brennan, Meghan B., Filutowicz, Hanna I., O'Brien, Kevin, Korthauer, Keegan D., Schultz-Cherry, Stacey, Klein, Bruce S. |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
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| Popis: |
CD4(+) T cells are the key players of vaccine resistance to fungi. The generation of effective T cell-based vaccines requires an understanding of how to induce and maintain CD4(+) T cells and memory. The kinetics of fungal antigen (Ag)-specific CD4(+) T cell memory development has not been studied due to the lack of any known protective epitopes and clonally restricted T cell subsets with complementary T cell receptors (TCRs). Here, we investigated the expansion and function of CD4(+) T cell memory after vaccination with transgenic (Tg) Blastomyces dermatitidis yeasts that display a model Ag, Eα-mCherry (Eα-mCh). We report that Tg yeast led to Eα display on Ag-presenting cells and induced robust activation, proliferation, and expansion of adoptively transferred TEa cells in an Ag-specific manner. Despite robust priming by Eα-mCh yeast, antifungal TEa cells recruited and produced cytokines weakly during a recall response to the lung. The addition of exogenous Eα-red fluorescent protein (RFP) to the Eα-mCh yeast boosted the number of cytokine-producing TEa cells that migrated to the lung. Thus, model epitope expression on yeast enables the interrogation of Ag presentation to CD4(+) T cells and primes Ag-specific T cell activation, proliferation, and expansion. However, the limited availability of model Ag expressed by Tg fungi during T cell priming blunts the downstream generation of effector and memory T cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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