Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor
Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor
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DOI：
10.1016/s1074-7613(00)80089-8
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发表时间：
1999-08-01
期刊：
影响因子：
32.4
通讯作者：
Honjo, T
中科院分区：
文献类型：
--
作者：
Nishimura, H;Nose, M;Honjo, T
PD-1是一个55 kDa的跨膜蛋白，含有基于免疫受体酪氨酸的抑制基序，激活后在淋巴细胞和单核细胞中被诱导。老年C57BL/6(B6)-PD-1(-/-)同源基因小鼠自发发生狼疮样增殖性关节炎和以IgG3沉积为主的肾小球肾炎，并通过引入Fas突变(LPR)显著加速。在H-2(b/d)背景的2C-TCR(anti-H-2L(D))转基因小鼠中引入PD-1零突变导致慢性系统性移植物抗宿主样疾病。此外，CD8(+)2C-TCR+PD-1(-/-)细胞在体外对H-2(D)同种异体细胞有明显的促增殖作用。综上所述，我们认为PD-1作为免疫反应的负性调节因子参与了外周自身耐受的维持。
PD-1, a 55 kDa transmembrane protein containing an immunoreceptor tyrosine-based inhibitory motif, is induced in lymphocytes and monocytic cells following activation. Aged C57BL/6(B6)-PD-1(-/-) congenic mice spontaneously developed characteristic lupus-like proliferative arthritis and glomerulonephritis with predominant IgG3 deposition, which were markedly accelerated by introduction of a Fas mutation (lpr). Introduction of a PD-1 null mutation into the 2C-TCR (anti-H-2L(d)) transgenic mice of the H-2(b/d) background resulted in the chronic and systemic graft-versus-host-like disease. Furthermore, CD8(+)2C-TCR+PD-1(-/-) cells exhibited markedly augmented proliferation in vitro in response to H-2(d) allogenic cells. Collectively, it is suggested that PD-1 is involved in the maintenance of peripheral self-tolerance by serving as a negative regulator of immune responses.