1. Academic Validation
  2. Granzyme B Is an Essential Mediator in CD8+ T Cell Killing of Theileria parva-Infected Cells

Granzyme B Is an Essential Mediator in CD8+ T Cell Killing of Theileria parva-Infected Cells

  • Infect Immun. 2018 Dec 19;87(1):e00386-18. doi: 10.1128/IAI.00386-18.
Jie Yang 1 Alan Pemberton 1 W Ivan Morrison 2 Tim Connelley 1
Affiliations

Affiliations

  • 1 The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
  • 2 The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom ivan.morrison@roslin.ed.ac.uk.
Abstract

There is established evidence that cytotoxic CD8+ T cells are important mediators of immunity against the bovine intracellular protozoan Parasite Theileria parva However, the mechanism by which the specific CD8+ T cells kill parasitized cells is not understood. Although the predominant pathway used by human and murine CD8+ T cells to kill pathogen-infected cells is granule exocytosis, involving the release of perforin and granzyme B, there is to date a lack of published information on the biological activities of bovine granzyme B. The present study set out to define the functional activities of bovine granzyme B and determine its role in mediating the killing of T. parva-parasitized cells. DNA constructs encoding functional and nonfunctional forms of bovine granzyme B were produced, and the proteins expressed in Cos-7 cells were used to establish an enzymatic assay to detect and quantify the expression of functional granzyme B protein. Using this assay, the levels of killing of different T. parva-specific CD8+ T cell clones were found to be significantly correlated with the levels of granzyme B protein but not the levels of mRNA transcript expression. Experiments using inhibitors specific for perforin and granzyme B confirmed that CD8+ T cell killing of parasitized cells is dependent on granule exocytosis and, specifically, granzyme B. Further studies showed that the granzyme B-mediated death of parasitized cells is independent of caspases and that granzyme B activates the proapoptotic molecule Bid.

Keywords

T cells; Theileria parva; cattle; cytotoxicity; granzyme B; substrate specificity.

Figures
Products
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    Product Name
    Description
    Target
    Research Area
  • HY-101297
    ≥98.0%, Caspase-8抑制剂