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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Human T regulatory cells can use the perforin pathway to cause autologous target cell death.

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.[1]


  1. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Grossman, W.J., Verbsky, J.W., Barchet, W., Colonna, M., Atkinson, J.P., Ley, T.J. Immunity (2004) [Pubmed]
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