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Am J Pathol. 2019 Jul 2. pii: S0002-9440(19)30240-8. doi: 10.1016/j.ajpath.2019.04.018. [Epub ahead of print]

Penetration of CD8+ Cytotoxic T Cells into Large Target, Tissue Cysts of Toxoplasma gondii, Leads to Its Elimination.

Author information

1
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky.
2
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
3
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky; Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia. Electronic address: yasu.suzuki@uky.edu.

Abstract

CD8+ cytotoxic T cells kill target cells through direct cell-cell contact. However, it remains unclear how these T cells eliminate a target of large mass. We investigated how CD8+ T cells remove tissue cysts of Toxoplasma gondii, which can grow to the size of >50 μm in diameter within infected cells. Notably, immunohistologic analyses in the brains of infected mice visualized the presence of numbers of CD8+ immune T cells that had migrated halfway through the cyst wall as well as T cells located fully within the cysts. Perforin was required for their invasion and cyst elimination. Cysts invaded by the T cells displayed morphologic deterioration and destruction. Within these deteriorated cysts, granular structures intensely positive for granzyme B were detected in association with T. gondii bradyzoites. Furthermore, the bradyzoites within the destroyed cysts were located within accumulated ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia and Ly6C+ macrophages, suggesting that these phagocytes had phagocytosed those organisms for their eradication. The present study uncovered a previously unappreciated capability of CD8+ cytotoxic T cells to penetrate into a large target, T. gondii cysts, for their elimination. This invasive capability of CD8+ cytotoxic T cells in collaboration with phagocytes appears to be a powerful effector mechanism that functions against not only T. gondii cysts but also other large targets, including solid cancers.

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