title: 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.
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.
authors: Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA. mwuethri@wisc.edu
authors: Marcel
authors: M
authors: Wüthrich
authors: Karen
authors: K
authors: Ersland
authors: John C
authors: JC
authors: Pick-Jacobs
authors: Benjamin H
authors: BH
authors: Gern
authors: Christopher A
authors: CA
authors: Frye
authors: Thomas D
authors: TD
authors: Sullivan
authors: Meghan B
authors: MB
authors: Brennan
authors: Hanna I
authors: HI
authors: Filutowicz
authors: Kevin
authors: K
authors: O'Brien
authors: Keegan D
authors: KD
authors: Korthauer
authors: Stacey
authors: S
authors: Schultz-Cherry
authors: Bruce S
authors: BS
authors: Klein
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000235:genetics / Q000378:metabolism*; D001758:Blastomyces / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008168:Lung / Q000166:cytology; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism
chemical_list: D000946:Antigens, Fungal; D005656:Fungal Proteins; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens