TY - JOUR
T1 - Functional roles for granzymes in murine epidermal γδ T-cell-mediated killing of tumor targets
AU - Mohamadzadeh, Mansour
AU - McGuire, Michael J.
AU - Smith, Donald J.
AU - Gaspari, Anthony A.
AU - Bergstresser, Paul R.
AU - Takashima, Akira
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
KW - Cytotoxicity
KW - Dendritic epidermal T cells
KW - Proteases
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U2 - 10.1111/1523-1747.ep12365634
DO - 10.1111/1523-1747.ep12365634
M3 - Article
C2 - 8875959
AN - SCOPUS:0029801340
SN - 0022-202X
VL - 107
SP - 738
EP - 742
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -