Functional roles for granzymes in murine epidermal gamma(delta) T-cell-mediated killing of tumor targets.
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 gamma(delta) 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.
Mohamadzadeh
M
M
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, USA.
McGuire
M J
MJ
Smith
D J
DJ
Gaspari
A A
AA
Bergstresser
P R
PR
Takashima
A
A
D000818:Animals; D003602:Cytotoxicity, Immunologic; D053938:DNA Fragmentation; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D053804:Granzymes; D051379:Mice; D008808:Mice, Inbred CBA; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D012697:Serine Endopeptidases / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases