[HTML][HTML] Penetration of CD8+ cytotoxic T cells into large target, tissue cysts of Toxoplasma gondii, leads to its elimination

A Tiwari, R Hannah, J Lutshumba, E Ochiai… - The American journal of …, 2019 - Elsevier
A Tiwari, R Hannah, J Lutshumba, E Ochiai, LM Weiss, Y Suzuki
The American journal of pathology, 2019Elsevier
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 …
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.
Elsevier