title: Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance.
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.
authors.affiliation: Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Cao
authors.forename: Sheng F
authors.initials: SF
authors.lastname: Cai
authors.forename: Todd A
authors.initials: TA
authors.lastname: Fehniger
authors.forename: Jiling
authors.initials: J
authors.lastname: Song
authors.forename: Lynne I
authors.initials: LI
authors.lastname: Collins
authors.forename: David R
authors.initials: DR
authors.lastname: Piwnica-Worms
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D053804:Granzymes / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D018448:Models, Immunological; D009374:Neoplasms, Experimental / Q000276:immunology*; D054353:Perforin / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D054353:Perforin; D053804:Granzymes