Human T regulatory cells can use the perforin pathway to cause autologous target cell death
Human T regulatory cells can use the perforin pathway to cause autologous target cell death
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DOI：
10.1016/j.immuni.2004.09.002
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发表时间：
2004-10-01
期刊：
影响因子：
32.4
通讯作者：
Ley, TJ
中科院分区：
文献类型：
--
作者：
Grossman, WJ;Verbsky, JW;Ley, TJ
细胞毒性T淋巴细胞和自然杀伤细胞利用穿孔素/颗粒酶途径来杀伤病毒感染细胞和肿瘤细胞。对该途径至关重要的基因发生突变与多种人类疾病相关。CD4(+)调节性T（Treg）细胞在免疫病理过程的控制中已显得非常重要。我们先前已表明，人类适应性Treg细胞优先表达颗粒酶B，并能以穿孔素依赖的方式杀伤同种异体靶细胞。在此，我们证明活化的人类CD4(+)CD25(+)天然Treg细胞表达颗粒酶A，但颗粒酶B的表达量极少。此外，两种Treg亚型对自体靶细胞均表现出穿孔素依赖的细胞毒性，这些靶细胞包括活化的CD4(+)和CD8(+) T细胞、CD14(+)单核细胞以及未成熟和成熟的树突状细胞。这种细胞毒性依赖于CD18黏附相互作用，但不依赖于Fas/FasL。我们的研究结果表明，穿孔素/颗粒酶途径是Treg细胞可用于控制免疫应答的机制之一。
Cytotoxic T lymphocytes and natural killer cells use the perforin/granzyme pathway to kill virally infected cells and tumor cells. Mutations in genes important for this pathway are associated with several human diseases. CD4(+) T regulatory (Treg) cells have emerged as important in the control of immunopathological processes. We have previously shown that human adaptive Treg cells preferentially express granzyme B and can kill allogeneic target cells in a perforin-dependent manner. Here, we demonstrate that activated human CD4(+)CD25(+) natural Treg cells express granzyme A but very little granzyme B. Furthermore, both Treg sub-types display perforin-dependent cytotoxicity against autologous target cells, including activated CD4(+) and CD8(+) T cells, CD14(+) monocytes, and both immature and mature dendritic cells. This cytotoxicity is dependent on CD18 adhesive interactions but is independent of Fas/FasL. Our findings suggest that the perforin/granzyme pathway is one of the mechanisms that Treg cells can use to control immune responses.