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

Ashish Tiwari, Rancie Hannah, J. Lutshumba, Eri Ochiai, Louis M. Weiss, Yasuhiro Suzuki

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1594-1607
Number of pages14
JournalAmerican Journal of Pathology
Volume189
Issue number8
DOIs
StatePublished - Aug 2019

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Toxoplasma
Cysts
T-Lymphocytes
Phagocytes
Granzymes
Perforin
Microglia
Phagocytosis
Macrophages
Calcium
Brain

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Penetration of CD8+ Cytotoxic T Cells into Large Target, Tissue Cysts of Toxoplasma gondii, Leads to Its Elimination. / Tiwari, Ashish; Hannah, Rancie; Lutshumba, J.; Ochiai, Eri; Weiss, Louis M.; Suzuki, Yasuhiro.

In: American Journal of Pathology, Vol. 189, No. 8, 08.2019, p. 1594-1607.

Research output: Contribution to journalArticle

Tiwari, Ashish ; Hannah, Rancie ; Lutshumba, J. ; Ochiai, Eri ; Weiss, Louis M. ; Suzuki, Yasuhiro. / Penetration of CD8+ Cytotoxic T Cells into Large Target, Tissue Cysts of Toxoplasma gondii, Leads to Its Elimination. In: American Journal of Pathology. 2019 ; Vol. 189, No. 8. pp. 1594-1607.
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