First Author | Tiwari A | Year | 2019 |
Journal | Am J Pathol | Volume | 189 |
Issue | 8 | Pages | 1594-1607 |
PubMed ID | 31301754 | Mgi Jnum | J:282085 |
Mgi Id | MGI:6370078 | Doi | 10.1016/j.ajpath.2019.04.018 |
Citation | Tiwari A, et al. (2019) Penetration of CD8(+) Cytotoxic T Cells into Large Target, Tissue Cysts of Toxoplasma gondii, Leads to Its Elimination. Am J Pathol 189(8):1594-1607 |
abstractText | 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 mum 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. |