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

William J. Grossman, James W. Verbsky, Winfried Barchet, Marco Colonna, John P. Atkinson, Timothy J. Ley

Research output: Contribution to journalArticlepeer-review

677 Scopus citations


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.

Original languageEnglish
Pages (from-to)589-601
Number of pages13
Issue number4
StatePublished - Oct 2004

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