| First Author | W?thrich M | Year | 2012 |
| Journal | Infect Immun | Volume | 80 |
| Issue | 2 | Pages | 787-97 |
| PubMed ID | 22124658 | Mgi Jnum | J:180817 |
| Mgi Id | MGI:5307942 | Doi | 10.1128/IAI.05326-11 |
| Citation | Wuthrich M, et al. (2012) 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. Infect Immun 80(2):787-97 |
| abstractText | 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, Ealpha-mCherry (Ealpha-mCh). We report that Tg yeast led to Ealpha 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 Ealpha-mCh yeast, antifungal TEa cells recruited and produced cytokines weakly during a recall response to the lung. The addition of exogenous Ealpha-red fluorescent protein (RFP) to the Ealpha-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. |
