Izquierdo M, Grandien A, Criado L M, Robles S, Leonardo E, Albar J P, de Buitrago G G, Martínez-A C
Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus de Cantoblanco, E-28049, Madrid, Spain.
EMBO J. 1999 Jan 4;18(1):156-66. doi: 10.1093/emboj/18.1.156.
Clonal deletion in the thymus by apoptosis is involved in purging the immune system of self-reactive T lymphocytes (negative selection). Cysteine proteases (caspases) belonging to the CPP32 family are activated during this process. We have produced transgenic mice expressing baculovirus p35, a broad-range caspase inhibitor. Thymocytes from p35 transgenic mice were resistant in vitro to several apoptosis-inducing agents; this resistance correlated with the inhibition of CPP32-like activity. Negative selection in vivo of thymocytes triggered by two exogenous antigens, staphylococcal enterotoxin B superantigen and an antigenic peptide in the F5 T-cell receptor transgenic model, was specifically inhibited in p35 transgenic mice. Our results provide direct evidence for caspase involvement in negative selection during thymocyte development.
通过凋亡实现的胸腺中的克隆清除参与清除免疫系统中的自身反应性T淋巴细胞（阴性选择）。在此过程中，属于CPP32家族的半胱氨酸蛋白酶（胱天蛋白酶）被激活。我们制备了表达杆状病毒p35（一种广谱胱天蛋白酶抑制剂）的转基因小鼠。来自p35转基因小鼠的胸腺细胞在体外对几种凋亡诱导剂具有抗性；这种抗性与CPP32样活性的抑制相关。在F5 T细胞受体转基因模型中，由两种外源性抗原（葡萄球菌肠毒素B超抗原和一种抗原肽）触发的胸腺细胞在体内的阴性选择在p35转基因小鼠中受到特异性抑制。我们的结果为胱天蛋白酶参与胸腺细胞发育过程中的阴性选择提供了直接证据。
