Salomon B, Rhee L, Bour-Jordan H, Hsin H, Montag A, Soliven B, Arcella J, Girvin A M, Padilla J, Miller S D, Bluestone J A
The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
J Exp Med. 2001 Sep 3;194(5):677-84. doi: 10.1084/jem.194.5.677.
An increasing number of studies have documented the central role of T cell costimulation in autoimmunity. Here we show that the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain, deficient in B7-2 costimulation, is protected from diabetes but develops a spontaneous autoimmune peripheral polyneuropathy. All the female and one third of the male mice exhibited limb paralysis with histologic and electrophysiologic evidence of severe demyelination in the peripheral nerves beginning at 20 wk of age. No central nervous system lesions were apparent. The peripheral nerve tissue was infiltrated with dendritic cells, CD4(+), and CD8(+) T cells. Finally, CD4(+) T cells isolated from affected animals induced the disease in NOD.SCID mice. Thus, the B7-2-deficient NOD mouse constitutes the first model of a spontaneous autoimmune disease of the peripheral nervous system, which has many similarities to the human disease, chronic inflammatory demyelinating polyneuropathy (CIDP). This model demonstrates that NOD mice have "cryptic" autoimmune defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway.
越来越多的研究证明了T细胞共刺激在自身免疫中的核心作用。在此我们表明，缺乏B7-2共刺激的自身免疫性糖尿病易感非肥胖糖尿病（NOD）小鼠品系可预防糖尿病，但会发生自发性自身免疫性周围多神经病。所有雌性小鼠和三分之一的雄性小鼠在20周龄时出现肢体麻痹，组织学和电生理学证据表明外周神经存在严重脱髓鞘。未发现明显的中枢神经系统病变。外周神经组织中有树突状细胞、CD4(+)和CD8(+) T细胞浸润。最后，从患病动物分离出的CD4(+) T细胞在NOD.SCID小鼠中诱发了该病。因此，B7-2缺陷的NOD小鼠构成了首个外周神经系统自发性自身免疫性疾病模型，该模型与人类疾病慢性炎症性脱髓鞘性多发性神经病（CIDP）有许多相似之处。该模型表明，NOD小鼠具有“隐匿性”自身免疫缺陷，在CD28/B7-2共刺激途径被选择性破坏后可向神经组织极化。
