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 journalArticlepeer-review

11 Scopus citations

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

Bibliographical note

Funding Information:
Supported, in part, by NIH grants AI095032 (Y.S.), AI134323 (Y.S.), and AI136821 (Y.S.). Supported, in part, by NIH grants AI095032 (Y.S.), AI134323 (Y.S.), and AI136821 (Y.S.). We thank Dr. Thomas Wilkop (Light Microscopy Core Facility at the University of Kentucky College of Medicine) for assistance in taking images in immunofluorescence-stained sections. Supported, in part, by NIH grants AI095032 (Y.S.), AI134323 (Y.S.), and AI136821 (Y.S.).

Publisher Copyright:
© 2019 American Society for Investigative Pathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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