The role of protease-activated receptor 1 signaling in CD8 T cell effector functions
Hui Chen,
Mindy Smith,
Jasmin Herz,
Tong Li,
Rebecca Hasley,
Cecile Le Saout,
Ziang Zhu,
Jie Cheng,
Andres Gronda,
José A. Martina,
Pablo M. Irusta,
Tatiana Karpova,
Dorian B. McGavern,
Marta Catalfamo
Affiliations
Hui Chen
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Mindy Smith
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Jasmin Herz
Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Tong Li
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA
Rebecca Hasley
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Cecile Le Saout
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Ziang Zhu
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA
Jie Cheng
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA
Andres Gronda
Department of Human Science, Georgetown University, Washington, DC, USA
José A. Martina
Cell and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Pablo M. Irusta
Department of Human Science, Georgetown University, Washington, DC, USA
Tatiana Karpova
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Dorian B. McGavern
Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Marta Catalfamo
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA; Corresponding author
Summary: CD8 T cells are essential for adaptive immunity against viral infections. Protease activated receptor 1 (PAR1) is expressed by CD8 T cells; however, its role in T cell effector function is not well defined. Here we show that in human CD8 T cells, PAR1 stimulation accelerates calcium mobilization. Furthermore, PAR1 is involved in cytotoxic T cell function by facilitating granule trafficking via actin polymerization and repositioning of the microtubule organizing center (MTOC) toward the immunological synapse. In vivo, PAR1−/− mice have reduced cytokine-producing T cells in response to a lymphocytic choriomeningitis virus (LCMV) infection and fail to efficiently control the virus. Specific deletion of PAR1 in LCMV GP33-specific CD8 T cells results in reduced expansion and diminished effector function. These data demonstrate that PAR1 plays a role in T cell activation and function, and this pathway could represent a new therapeutic strategy to modulate CD8 T cell effector function.
