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 utiliz...
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Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2007-10, Vol.27 (4), p.635-646 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2007.08.014 |