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

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02425464
Contributor : Rogerio Amino <>
Submitted on : Monday, December 30, 2019 - 3:30:59 PM
Last modification on : Monday, January 13, 2020 - 5:08:18 PM

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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, American Society for Microbiology, 2018, 86 (4), pp.e00717-17. ⟨10.1128/IAI.00717-17⟩. ⟨pasteur-02425464⟩

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