Limited Model Antigen Expression by Transgenic Fungi Induces Disparate Fates during Differentiation of Adoptively Transferred T Cell Receptor Transgenic CD4 + T Cells: Robust Activation and Proliferation with Weak Effector Function during Recall
| Autor: | Benjamin H. Gern, John C. Pick-Jacobs, Karen Ersland, Thomas D. Sullivan, Christopher A. Frye, Marcel Wüthrich, Bruce S. Klein, Keegan Korthauer, Meghan B. Brennan, Kevin O'Brien, Hanna I. Filutowicz, Stacey L. Schultz-Cherry |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Infection and Immunity. 80:787-797 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.05326-11 |
| 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 |
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