1. 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.
- Author
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Wüthrich M, Ersland K, Pick-Jacobs JC, Gern BH, Frye CA, Sullivan TD, Brennan MB, Filutowicz HI, O'Brien K, Korthauer KD, Schultz-Cherry S, and Klein BS
- Subjects
- Animals, Antigens, Fungal genetics, Blastomyces immunology, Cell Differentiation, Cell Movement, Fungal Proteins genetics, Gene Expression Regulation, Fungal, Lung cytology, Lung Diseases, Fungal immunology, Lung Diseases, Fungal microbiology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Thy-1 Antigens genetics, Thy-1 Antigens metabolism, Antigens, Fungal metabolism, Blastomyces genetics, CD4-Positive T-Lymphocytes physiology, Fungal Proteins metabolism, Receptors, Antigen, T-Cell genetics
- Abstract
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.
- Published
- 2012
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