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Published on: March 5, 2019
Human yeast-specific CD8 T lymphocytes show a nonclassical effector molecule profile
Tanja Breinig1, Nicoletta Scheller, Birgit Glombitza
1Junior Research Group for Virology/Immunology, Saarland University, 66421, Homburg, Germany. breinig@cs.uni-saarland.de
Abstract:
Pathogenic yeast and fungi represent a major group of human pathogens. The consequences of infections are diverse and range from local, clinically uncomplicated mycosis of the skin to systemic, life-threatening sepsis. Despite extensive MHC class I-restricted frequencies of yeast-specific CD8 T lymphocytes in healthy individuals and the essential role of the cell-mediated immunity in controlling infections, the characteristics and defense mechanisms of antifungal effector cells are still unclear. Here, we describe the direct analysis of yeast-specific CD8 T lymphocytes in whole blood from healthy individuals. They show a unique, nonclassical phenotype expressing granulysin and granzyme K in lytic granules instead of the major effector molecules perforin and granzyme B. After stimulation in whole blood, yeast-specific CD8 T cells degranulated and, upon cultivation in the presence of IL-2, their granula were refilled with granulysin rather than with perforin and granzyme B. Moreover, yeast-specific stimulation through dendritic cells but not by yeast cells alone led to degranulation of the effector cells. As granulysin is the only effector molecule in lytic granules known to have antifungal properties, our data suggest yeast-specific CD8 T cells to be a nonclassical effector population whose antimicrobial effector machinery seems to be tailor-made for the efficient elimination of fungi as pathogens.
Insights
Researchers discovered a unique type of CD8 T cell in healthy individuals that targets yeast and fungi. These cells use granulysin, an antifungal molecule, to eliminate fungal pathogens, highlighting a novel defense mechanism against mycoses.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Pathogenic yeasts and fungi cause diverse human infections, from skin mycosis to life-threatening sepsis.
- Cell-mediated immunity is crucial for controlling fungal infections, but antifungal effector cell mechanisms remain unclear.
- Healthy individuals possess yeast-specific CD8 T lymphocytes, yet their precise function is not fully understood.
Purpose of the Study:
- To directly analyze yeast-specific CD8 T lymphocytes in whole blood from healthy individuals.
- To characterize the phenotype and effector molecules of these antifungal CD8 T cells.
- To elucidate the defense mechanisms employed by these cells against fungal pathogens.
Main Methods:
- Direct analysis of yeast-specific CD8 T lymphocytes in whole blood.
- Phenotypic characterization including expression of effector molecules.
- Stimulation assays using yeast and dendritic cells.
- Analysis of degranulation and granule content after stimulation and cultivation.
Main Results:
- Yeast-specific CD8 T cells exhibit a nonclassical phenotype, expressing granulysin and granzyme K, not perforin and granzyme B.
- These cells degranulate upon stimulation and refill granules with granulysin.
- Dendritic cell-mediated stimulation, but not yeast cells alone, induced effector cell degranulation.
Conclusions:
- Yeast-specific CD8 T cells represent a nonclassical effector population with a unique antimicrobial machinery.
- Granulysin, known for its antifungal properties, is the key effector molecule used by these cells.
- This suggests a specialized defense mechanism tailored for efficient elimination of fungi as pathogens.
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