Thymic stromal-cell abnormalities and dysregulated T-cell development in IL-2-deficient mice.
Thymic stromal-cell abnormalities and dysregulated T-cell development in IL-2-deficient mice.
复制标题
DOI：
10.1155/1998/19567
复制
发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Carding, S R
中科院分区：
文献类型：
--
作者：
Reya, T;Bassiri, H;Carding, S R
白介素2(IL-2)在T细胞发育中的作用尚不清楚。为了解决这个问题，我们研究了IL-2缺陷(IL-2-/-)小鼠胸腺发育异常和自身免疫紊乱的本质。出生4至5周后，IL-2-/-小鼠逐渐发展为胸腺疾病，导致胸腺细胞成熟中断。这种疾病的特征是细胞数量显著减少，未成熟的CD4-8-(双阴性；dN)和CD4+8+(双阳性；dp)胸腺细胞选择性丧失，胸腺基质细胞室有缺陷。免疫组织化学染色显示，不同年龄的无特定病原体和无细菌的IL-2-/-小鼠的胸腺切片显示皮质上皮细胞、表达MHC II类的细胞、单核细胞和巨噬细胞逐渐丧失。巨噬细胞数量的减少早在出生后1周就很明显。由于IL-2-/-胸腺细胞前体细胞在移植到正常胸腺时可以正常成熟，IL-2-/-小鼠的胸腺缺陷似乎是由于胸腺基质细胞之间的异常所致。这些结果强调了IL-2在维持胸腺细胞生长、发育和选择所必需的功能微环境中的作用。
The role that interleukin-2 (IL-2) plays in T-cell development is not known. To address this issue, we have investigated the nature of the abnormal thymic development and autoimmune disorders that occurs in IL-2-deficient (IL-2-/-) mice. After 4 to 5 weeks of birth, IL-2-/- mice progressively develop a thymic disorder resulting in the disruption of thymocyte maturation. This disorder is characterized by a dramatic reduction in cellularity, the selective loss of immature CD4-8- (double negative; DN) and CD4+8+ (double positive; DP) thymocytes and defects in the thymic stromal-cell compartment. Immunohistochemical staining of sections of thymuses from specific pathogen-free and germ-free IL-2-/- mice of various ages showed a progressive loss of cortical epithelial cells, MHC class II-expressing cells, monocytes, and macrophages. Reduced numbers of macrophages were apparent as early as 1 week after birth. Since IL-2-/- thymocyte progenitor populations could mature normally on transfer into a normal thymus, the thymic defect in IL-2-/- mice appears to be due to abnormalities among thymic stromal cells. These results underscore the role of IL-2 in maintaining functional microenvironments that are necessary to support thymocyte growth, development, and selection.