Nonspecific CD8 + T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8 + T Cell-Mediated Clusters against Malaria Liver-Stage Infection - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Infection and Immunity Année : 2018

Nonspecific CD8 + T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8 + T Cell-Mediated Clusters against Malaria Liver-Stage Infection

Résumé

CD8+ T cells are the major effector cells that protect against malaria liver-stage 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.

Dates et versions

pasteur-02425464 , version 1 (30-12-2019)

Identifiants

Citer

Masoud Akbari, Kazumi Kimura, Ganchimeg Bayarsaikhan, Daisuke Kimura, Mana Miyakoda, et al.. Nonspecific CD8 + T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8 + T Cell-Mediated Clusters against Malaria Liver-Stage Infection. Infection and Immunity, 2018, 86 (4), pp.e00717-17. ⟨10.1128/IAI.00717-17⟩. ⟨pasteur-02425464⟩

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