New Development of Multiple Autoimmune Diseases in Neonatally Thymectomized Autoimmune Mice

NZB/NZWF1(BWF1)和MRL/MP-1PR/1PR(MRL/1PR)小鼠自发地发展成一种类似于人类系统性红斑狼疮(SLE)的疾病。非肥胖糖尿病(NOD)小鼠是人类胰岛素依赖型糖尿病的模型，它会患上自身免疫性胰岛素炎。我们已经报道了器官局限性自身免疫性疾病的自发发展，如甲状腺炎、胃炎，在第3天胸腺切除(TX-3)标准小鼠，如BALB/c和A/J小鼠。这种自身免疫性疾病不会在TX-7小鼠身上发生。这项研究的目的是检查胸腺在各种自发发展成系统性红斑狼疮和胰腺炎的小鼠中的作用。TX-3、BWF1和MRL/1PR小鼠均出现肾小球肾炎和多发性关节炎。这些病变的发生率和严重程度与非TX小鼠几乎相同。在这些TX-3小鼠身上发现了器官甘油化的自身免疫性疾病，如胃炎和卵巢炎。共同表明，诱导全身和器官局限性自身免疫性疾病的效应性T细胞在新生儿早期就从胸腺外围消失了。在TX-3 NOD小鼠中发现多种器官局限性自身免疫性疾病。在TX-7和TX-14小鼠中也发现了这种自身免疫性疾病，表明胸腺功能异常。TX-3 NOD组小鼠的胰岛素炎症发生率和严重程度均低于未治疗组。从同基因正常小鼠获取的具有L3T4表型的脾T细胞可预防TX后自身免疫损伤。

NZB/NZWF1 (BWF1) and MRL/Mp-1pr/1pr (MRL/1pr) mice spontaneously develop a disorder resembling human systemic lupus erythematosus (SLE). The non-obese diabetic (NOD) mouse, a model of human insulin dependent diabetes mellitus, develops autoimmune insulitis. We have been reported that spontaneous development of organ-localized autoimmune diseases, such as thyroiditis, gastritis, in day 3 thymectomized (Tx-3) standard mice such as BALB/c and A/J mice. Such autoimmune diseases does not develop in Tx-7 mice. The purpose of this investigation was to examine the role of the thymus in the various mice that spontaneously developing SLE and insulitis. Development of glomerulonephritis and polyarthritis was found in Tx-3 BWF1 and MRL/1pr mice. The incidence and severity of these lesions were almost same to those of non-Tx mice. Organ-licolized autoimmune diseases, such as gastritis and oophoritis, were found in these Tx-3 mice. Together indicating that effector T cells for induction of both systemic and organ-localized autoimmune diseases were peripheralized from the thymus at early neonatal age. Multiple development of organ-localized autoimmune diseases were found in Tx-3 NOD mice. Such autoimmune diseases were also found in Tx-7 and Tx-14 mice indicating the functional abnormality of the thymus. The incidence and severity of insulitis in Tx-3 NOD mice were lower than those of untreated mice. Post-Tx autoimmune lesions were prevented by splenic T cells with L3T4 phenotype obtained from syngeneic normal mice.