[PDF][PDF] Human T regulatory cells can use the perforin pathway to cause autologous target cell death

WJ Grossman, JW Verbsky, W Barchet, M Colonna… - Immunity, 2004 - cell.com
WJ Grossman, JW Verbsky, W Barchet, M Colonna, JP Atkinson, TJ Ley
Immunity, 2004cell.com
Cytotoxic T lymphocytes and natural killer cells use the perforin/granzyme pathway to kill
virally infected cells and tumor cells. Mutations in genes important for this pathway are
associated with several human diseases. CD4+ T regulatory (Treg) cells have emerged as
important in the control of immunopathological processes. We have previously shown that
human adaptive Treg cells preferentially express granzyme B and can kill allogeneic target
cells in a perforin-dependent manner. Here, we demonstrate that activated human CD4+ …
Abstract
Cytotoxic T lymphocytes and natural killer cells use the perforin/granzyme pathway to kill virally infected cells and tumor cells. Mutations in genes important for this pathway are associated with several human diseases. CD4+ T regulatory (Treg) cells have emerged as important in the control of immunopathological processes. We have previously shown that human adaptive Treg cells preferentially express granzyme B and can kill allogeneic target cells in a perforin-dependent manner. Here, we demonstrate that activated human CD4+CD25+ natural Treg cells express granzyme A but very little granzyme B. Furthermore, both Treg subtypes display perforin-dependent cytotoxicity against autologous target cells, including activated CD4+ and CD8+ T cells, CD14+ monocytes, and both immature and mature dendritic cells. This cytotoxicity is dependent on CD18 adhesive interactions but is independent of Fas/FasL. Our findings suggest that the perforin/granzyme pathway is one of the mechanisms that Treg cells can use to control immune responses.
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