Functional roles for granzymes in murine epidermal γδ T-cell-mediated killing of tumor targets

Mansour Mohamadzadeh, Michael J. McGuire, Donald J. Smith, Anthony A. Gaspari, Paul R. Bergstresser, Akira Takashima

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Granzymes, a family of serine proteases contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells, play a critical role in killing tumor targets by triggering rapid breakdown of DNA and subsequent apoptosis. We have reported previously that dendritic epidermal T cells, which are skin-specific members of the tissue-type γδ T-cell family in mice, are capable of killing selected tumor cell lines. Here we report that short-term cultured dendritic epidermal T-cell lines contain significant N-alpha-benzyloxycarbonyl-L-Lys-thiobenzyl esterase activity, produce granzyme A protein, and express constitutively mRNA for granzymes A and B. Messenger RNA expression for granzyme B was also confirmed in freshly procured Thy-1+ epidermal cells (i.e., dendritic epidermal T cells). Finally, preincubation of dendritic epidermal T cell lines with a granzyme inhibitor, dichloroisocoumarin, but not with a cysteine protease inhibitor, E-64, abrogated completely their capacity to trigger DNA breakdown in YAC-1 target cells. These results reinforce the concept that dendritic epidermal T cells represent skin-resident killer cells that share several functional properties with conventional killer leukocytes, thereby playing a local immunosurveillance role against tumor development.

Original languageEnglish (US)
Pages (from-to)738-742
Number of pages5
JournalJournal of Investigative Dermatology
Volume107
Issue number5
DOIs
StatePublished - 1996

Keywords

  • Cytotoxicity
  • Dendritic epidermal T cells
  • Proteases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Mohamadzadeh, M., McGuire, M. J., Smith, D. J., Gaspari, A. A., Bergstresser, P. R., & Takashima, A. (1996). Functional roles for granzymes in murine epidermal γδ T-cell-mediated killing of tumor targets. Journal of Investigative Dermatology, 107(5), 738-742. https://doi.org/10.1111/1523-1747.ep12365634