Department of Immunology, Faculty of Medicine, Imperial College London, London W12 0NN, UK.
Immunol Rev. 2010 May;235(1):147-58. doi: 10.1111/j.0105-2896.2010.00892.x.
Serine proteases control a wide variety of physiological and pathological processes in multi-cellular organisms, including blood clotting, cancer, cell death, osmoregulation, tissue remodeling, and immunity to infection. Cytotoxic T lymphocytes (CTLs) are required for adaptive cell-mediated immunity to intracellular pathogens by killing infected cells and through the development of memory T cells. Serine proteases not only allow a CTL to kill but also impose homeostatic control on CTL number. Serine protease inhibitors (serpins) are the physiological regulators of serine proteases' activity. In this review, I discuss the role of serpins in controlling the recognition of antigen, effector function, and homeostatic control of CTLs through the inhibition of physiological serine protease targets. An emerging view of serpins is that they are important promoters of cellular viability through their inhibition of executioner proteases. This view is discussed in the context of the T-lymphocyte survival during effector responses and the development and persistence of long-lived memory T cells. Given the important role serpins play in CTL immunity, I discuss the potential for developing new immunotherapeutic approaches based directly on serpins or knowledge gained from identifying their physiologically relevant protease targets.
丝氨酸蛋白酶在多细胞生物中控制着广泛的生理和病理过程，包括血液凝固、癌症、细胞死亡、渗透调节、组织重塑和抗感染免疫。细胞毒性 T 淋巴细胞（CTL）通过杀死感染细胞和产生记忆 T 细胞，对细胞内病原体的适应性细胞介导免疫至关重要。丝氨酸蛋白酶不仅允许 CTL 杀死细胞，还对 CTL 数量施加了体内平衡控制。丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）是丝氨酸蛋白酶活性的生理调节剂。在这篇综述中，我讨论了丝氨酸蛋白酶通过抑制生理丝氨酸蛋白酶靶标，在控制抗原识别、效应功能和 CTL 体内平衡控制中的作用。丝氨酸蛋白酶在抑制执行蛋白酶方面是细胞活力的重要促进剂，这一观点正在形成。这一观点是在效应反应期间 T 淋巴细胞存活以及长寿命记忆 T 细胞的发展和持续存在的背景下进行讨论的。鉴于丝氨酸蛋白酶在 CTL 免疫中发挥的重要作用，我讨论了基于丝氨酸蛋白酶或从鉴定其生理相关蛋白酶靶标中获得的知识，直接开发新的免疫治疗方法的潜力。
