Infection and Immunity
Infection and Immunity
5 years ago

Non-specific CD8+ T cells and dendritic cells/macrophages participate in CD8+ T cell-mediated cluster formation against malaria liver-stage infection.

Masoud Akbari, Masao Yuda, Kazumi Kimura, Daisuke Kimura, Katsuyuki Yui, Smriti Juriasingani, Rogerio Amino, Mana Miyakoda, Ganchimeg Bayarsaikhan
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 prolonged interaction with these hepatocytes. We aimed to investigate roles of specific and non-specific 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 non-specific CD8+ T cells joined the cluster. However, non-specific 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. 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. Non-specific CD8+ T cells seem to play a limited role in protective immunity against Plasmodium parasites.

Publisher URL: http://doi.org/10.1128/IAI.00717-17

DOI: 10.1128/IAI.00717-17

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