Nat Rev Immunol. 2015 Jun;15(6):388-400. doi: 10.1038/nri3839.
A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin–granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.
细胞毒性淋巴细胞的一个定义特征是它们表达和调节分泌有效的毒素，包括形成孔的蛋白穿孔素和丝氨酸蛋白酶颗粒酶。直到最近，孔形成和颗粒酶转移到靶细胞的机制还知之甚少，但结构和细胞生物学的进展现在已经开始揭示穿孔素和颗粒酶之间的协同作用如何导致靶细胞死亡。这些和其他进展表明，穿孔素-颗粒酶途径具有惊人广泛的病理生理学作用，这对于理解免疫稳态和开发癌症和其他疾病的免疫疗法具有重要意义。特别是，我们开始定义和理解一系列与无法将活性穿孔素递送到靶细胞相关的人类疾病。在这篇综述中，我们讨论了对穿孔素和颗粒酶生物学的结构、细胞和临床方面的当前理解。
