Mechanismen der Interaktion von Mastzellen und T-Zellen bei viralen Infektionen
Immunologie
Zusammenfassung der Projektergebnisse
We investigated the role of MCs in the development of virus-specific CD8+ T cell responses using the well-characterized murine lymphocytic choriomeningitis virus (LCMV) model and the transgenic MasTRECK mice that contain the human diphtheria toxin receptor as an inducible MC-deficient model. Here, we report that MCs are essential for the activation and expansion of virus-specific CD8+ T cells. After MC depletion and subsequent LCMV infection, the CD8+ T cell effector phenotype and antiviral cytokine production were impaired at the peak of infection. Importantly, MC-deficient mice were unable to control the infection and exhibited significantly higher viral loads in the spleen and draining lymph nodes compared to that of wild type control mice. In the absence of MCs, dendritic cell (DC) activation was impaired upon LCMV infection and type-I interferon levels were reduced during the first days of infection. In summary, our results indicate that MCs play a pivotal role in the activation and antiviral functions of CD8+ T cells through proper DC activation. In addition, we can also report that Th2-polarized T cells lacking the transcription factor T-bet harbor strong immunomodulatory potential and suppress antigen-specific CD8+ T cells via IL-10.
Projektbezogene Publikationen (Auswahl)
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Th2 cells lacking T-bet suppress naive and memory T cell responses via IL- 10. Proc Natl Acad Sci USA. 2021 Feb 9;118(6):e2002787118
Melba Muñoz , Ahmed N Hegazy, Tobias M Brunner, Vivien Holecska , Roman M Marek , Anja Fröhlich , Max Löhning
