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In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages

Abstract : CD8(+) T cells are specialized cells of the adaptive immune system capable of finding and eliminating pathogen-infected cells. To date it has not been possible to observe the destruction of any pathogen by CD8(+) T cells in vivo. Here we demonstrate a technique for imaging the killing of liver-stage malaria parasites by CD8(+) T cells bearing a transgenic T cell receptor specific for a parasite epitope. We report several features that have not been described by in vitro analysis of the process, chiefly the formation of large clusters of effector CD8(+) T cells around infected hepatocytes. The formation of clusters requires antigen-specific CD8(+) T cells and signaling by G protein-coupled receptors, although CD8(+) T cells of unrelated specificity are also recruited to clusters. By combining mathematical modeling and data analysis, we suggest that formation of clusters is mainly driven by enhanced recruitment of T cells into larger clusters. We further show various death phenotypes of the parasite, which typically follow prolonged interactions between infected hepatocytes and CD8(+) T cells. These findings stress the need for intravital imaging for dissecting the fine mechanisms of pathogen recognition and killing by CD8(+) T cells.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02425479
Contributor : Rogerio Amino <>
Submitted on : Monday, December 30, 2019 - 3:44:58 PM
Last modification on : Monday, January 13, 2020 - 5:08:05 PM

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I. Cockburn, R. Amino, R. Kelemen, S. Kuo, S.-W. Tse, et al.. In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2013, 110 (22), pp.9090-9095. ⟨10.1073/pnas.1303858110⟩. ⟨pasteur-02425479⟩

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