Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance
Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance
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DOI：
10.1016/j.immuni.2007.08.014
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发表时间：
2007-10-01
期刊：
影响因子：
32.4
通讯作者：
Ley, Timothy J.
中科院分区：
文献类型：
--
作者：
Cao, Xuefang;Cai, Sheng F.;Ley, Timothy J.
颗粒酶B对于NK细胞和CD 8（+）T细胞杀伤其靶细胞的能力是重要的。然而，我们在这里表明，颗粒酶B缺陷小鼠清除同种异体和同基因肿瘤细胞系比野生型（WT）小鼠更有效。为了确定调节性T（Treg）细胞是否利用颗粒酶B来抑制针对这些肿瘤的免疫应答，我们检测了Treg细胞中颗粒酶B的表达和功能。颗粒酶B在初始Treg细胞中不表达，但在肿瘤环境中在5%-30%的CD 4（+）Foxp 3（+）Treg细胞中高度表达。将WT Treg细胞连续转移到颗粒酶B缺陷型小鼠中，而不是颗粒酶B或穿孔素缺陷型Treg细胞，部分恢复了对肿瘤生长的易感性;来源于肿瘤环境的Treg细胞可以以颗粒酶B和穿孔素依赖性方式诱导NK和CD 8 + T细胞死亡。因此，颗粒酶B和穿孔素与体内Treg细胞介导的肿瘤清除抑制相关。
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-cleficient 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.