1. Nonspecific CD8 + T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8 + T Cell-Mediated Clusters against Malaria Liver-Stage Infection
- Author
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Katsuyuki Yui, Rogerio Amino, Daisuke Kimura, Masoud Akbari, Kazumi Kimura, Ganchimeg Bayarsaikhan, Masao Yuda, Smriti Juriasingani, Mana Miyakoda, Division of Immunology [Nagasaki University], Department of Molecular Microbiology and Immunology [Nagasaki University, Japan], Graduate School of Biomedical Sciences [Nagasaki University, Japan], Nagasaki University-Nagasaki University-Graduate School of Biomedical Sciences [Nagasaki University, Japan], Nagasaki University-Nagasaki University, University of Western Ontario (UWO), Mie University Graduate School / Faculty of Medicine [Japan], Mie University, Infection et Immunité paludéennes - Malaria Infection and Immunity, Institut Pasteur [Paris] (IP), This work was supported by grants-in-aid for scientific research from the Japan Society for the Promotion of Science (25113717 and 15K15124) to K.Y., We thank Nobuka Kawamoto and Mikiyo Yoshida for their technical assistance., and Institut Pasteur [Paris]
- Subjects
0301 basic medicine ,MESH: Macrophages/immunology ,Chemokine ,MESH: Mice, Transgenic ,T cell ,Immunology ,malaria ,CD11c ,MESH: Liver Diseases, Parasitic/immunology ,CD8 T cells ,Biology ,liver ,Microbiology ,MESH: CD8-Positive T-Lymphocytes/immunology ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,medicine ,Cytotoxic T cell ,MESH: Animals ,IL-2 receptor ,dendritic cells ,MESH: Macrophages/metabolism ,MESH: CD8-Positive T-Lymphocytes/metabolism ,MESH: Mice ,MESH: Malaria/parasitology ,MESH: Dendritic Cells/metabolism ,MESH: Liver Diseases, Parasitic/diagnosis ,T-cell receptor ,MESH: Epitopes, T-Lymphocyte/immunology ,MESH: Hepatocytes/immunology ,imaging ,Molecular biology ,3. Good health ,MESH: Liver Diseases, Parasitic/parasitology ,MESH: Lymphocyte Activation/immunology ,MESH: Malaria/diagnosis ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,biology.protein ,MESH: Malaria/immunology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Parasitology ,MESH: Disease Models, Animal ,CD8 ,030215 immunology ,MESH: Dendritic Cells/immunology - Abstract
CD8+ T cells are the major effector cells that protect against malaria liverstage infection, forming clusters around Plasmodium-infected hepatocytes and eliminating parasites after a prolonged interaction with these hepatocytes. We aimed to investigate the roles of specific and nonspecific CD8+ T cells in cluster formation and protective immunity. To this end, we used Plasmodium berghei ANKA expressing ovalbumin as well as CD8+ T cells from transgenic mice expressing a T cell receptor specific for ovalbumin (OT-I) and CD8+ T cells specific for an unrelated antigen, respectively. While antigen-specific CD8+ T cells were essential for cluster formation, both antigen-specific and nonspecific CD8+ T cells joined the clusters. However, nonspecific CD8+ T cells did not significantly contribute to protective immunity. In the livers of infected mice, specific CD8+ T cells expressed high levels of CD25, compatible with a local, activated effector phenotype. In vivo imaging of the liver revealed that specific CD8+ T cells interact with CD11c+ cells around infected hepatocytes. The depletion of CD11c+ cells virtually eliminated the clusters in the liver, leading to a significant decrease in protection. These experiments reveal an essential role of hepatic CD11c+ dendritic cells and presumably macrophages in the formation of CD8+ T cell clusters around Plasmodium-infected hepatocytes. Once cluster formation is triggered by parasite-specific CD8+ T cells, specific and unrelated activated CD8+ T cells join the clusters in a chemokine- and dendritic cell-dependent manner. Nonspecific CD8+ T cells seem to play a limited role in protective immunity against Plasmodium parasites., Infection and Immunity, 86(4), 00717-17; 2018
- Published
- 2018