Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance.
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.
Cao
Xuefang
X
Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cai
Sheng F
SF
Fehniger
Todd A
TA
Song
Jiling
J
Collins
Lynne I
LI
Piwnica-Worms
David R
DR
Ley
Timothy J
TJ
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
D054353:Perforin; D053804:Granzymes