Ikehara S, Tanaka H, Nakamura T, Furukawa F, Inoue S, Sekita K, Shimizu J, Hamashima Y, Good R A
Thymus. 1985;7(1):25-36.
The relationship between thymic abnormalities and development of autoimmune diseases was studied in MRL/l and NZB/NZW F1 (NZB/W F1) mice. Thymic abnormalities, including plasma cell infiltration into the thymus, were observed in 25% of MRL/l mice as early as 1 mo and in all mice after 2.5 mo. The thymic abnormalities preceded both infiltration of lymphoid cells into the kidney and salivary glands, and also preceded an increase in the titer of circulating immune complexes (CIC). When MRL/l and NZB/W F1 mice were divided into two groups for each strain at the critical age when the mice had begun to show thymic abnormalities, the group with abnormal thymuses showed more marked pathological findings in other organs and a higher level of CIC than the group with more normal appearing thymus. In addition, the group with abnormal thymus demonstrated lower responsiveness of their lymphocytes in mixed-lymphocyte culture than the group with normal thymus. Thymus grafts from donors of autoimmune or non-autoimmune strains into nude mice revealed that thymic functions, reconstitutive of immunologic parameters of nude mice, are rapidly lost with age. These results suggest that morphological and functional abnormalities of the thymus are involved in the pathogenesis of autoimmune diseases.
在MRL/l和NZB/NZW F1（NZB/W F1）小鼠中研究了胸腺异常与自身免疫性疾病发展之间的关系。早在1个月时，25%的MRL/l小鼠就观察到胸腺异常，包括浆细胞浸润胸腺，2.5个月后所有小鼠均出现胸腺异常。胸腺异常先于淋巴细胞浸润肾脏和唾液腺，也先于循环免疫复合物（CIC）滴度升高。当MRL/l和NZB/W F1小鼠在开始出现胸腺异常的关键年龄时，按每个品系分为两组，胸腺异常组在其他器官中表现出比胸腺外观更正常的组更明显的病理表现，且CIC水平更高。此外，胸腺异常组在混合淋巴细胞培养中其淋巴细胞的反应性低于胸腺正常组。将自身免疫或非自身免疫品系供体的胸腺移植到裸鼠中发现，重建裸鼠免疫参数的胸腺功能会随着年龄增长而迅速丧失。这些结果表明，胸腺的形态和功能异常与自身免疫性疾病的发病机制有关。
