New Development of Multiple Autoimmune Diseases in Neonatally Thymectomized Autoimmune Mice

NZB/NZWF1 （BWF1）和MRL/Mp-1pr/1pr （MRL/1pr）小鼠自发发生类似于人系统性红斑狼疮（SLE）的疾病。非肥胖糖尿病（NOD）小鼠，人类胰岛素依赖型糖尿病的模型，发展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，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小鼠中自发发展。这种自身免疫性疾病在Tx-7小鼠中不会发生。本研究的目的是研究胸腺在自发发展为SLE和胰岛素炎的各种小鼠中的作用。在Tx-3 BWF1和MRL/1pr小鼠中发现肾小球肾炎和多发性关节炎的发展。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小鼠中发现了器官化的自身免疫性疾病，如胃炎和卵巢炎。这两项研究表明，新生儿早期胸腺外周化了诱导全身和器官局部自身免疫性疾病的效应T细胞。在Tx-3 NOD小鼠中发现了多种器官局限性自身免疫性疾病的发展。在Tx-7和Tx-14小鼠中也发现了这些自身免疫性疾病，表明胸腺功能异常。Tx-3 NOD小鼠胰岛素的发生率和严重程度均低于未治疗小鼠。从同基因正常小鼠获得的L3T4表型脾T细胞可预防tx后自身免疫性病变。

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.