Granzyme B and Perforin Are Important for Regulatory T Cell-Mediated Suppression of Tumor Clearance

Xuefang Cao, Sheng F. Cai, Todd A. Fehniger, Jiling Song, Lynne I. Collins, David R. Piwnica-Worms, Timothy J. Ley

Research output: Contribution to journalArticlepeer-review

540 Scopus citations

Abstract

Granzyme B is important for the ability of NK cells and CD8+ T cells to kill their targets. However, we showed here that granzyme B-deficient mice clear both allogeneic and syngeneic tumor cell lines more efficiently than do wild-type (WT) mice. To determine whether regulatory T (Treg) cells utilize granzyme B to suppress immune responses against these tumors, we examined the expression and function of granzyme B in Treg cells. Granzyme B was not expressed in naive Treg cells but was highly expressed in 5%-30% of CD4+Foxp3+ Treg cells in the tumor environment. Adoptive transfer of WT Treg cells, but not granzyme B- or perforin-deficient Treg cells, into granzyme B-deficient mice partially restored susceptibility to tumor growth; Treg cells derived from the tumor environment could induce NK and CD8+ T cell death in a granzyme B- and perforin-dependent fashion. Granzyme B and perforin are therefore relevant for Treg cell-mediated suppression of tumor clearance in vivo.

Original languageEnglish
Pages (from-to)635-646
Number of pages12
JournalImmunity
Volume27
Issue number4
DOIs
StatePublished - Oct 26 2007

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

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