Beschorner W E, Namnoum J D, Hess A D, Shinn C A, Santos G W
Am J Pathol. 1987 Mar;126(3):487-96.
Cyclosporin A (CsA) is known to diminish the size of the thymus, especially the thymic medulla. The significance of these changes is not presently understood. This study reveals several immunopathologic changes induced in the thymic medulla by CsA (15 mg/kg/day). The weight and relative size of the thymus dramatically and rapidly involutes, with marked changes observed in 1 week. The medullary thymocytes show segregation of rat T-cell phenotypes as seen in control rats, but the number of such cells is markedly reduced in accordance with the medullary remnant. This is consistent with a maturational arrest of thymocytes. The medullary epithelium was assessed directly by irradiating the control or CsA-treated rats 2 days prior to sacrifice. The epithelium of Hassall's corpuscles was essentially absent in CsA-treated rats but prominent in control rats. The cortical epithelial cells were preserved. Stains for Ia antigen with the anti-OX4 antibody show little change in expression by cortical epithelium, but a marked reduction in the Ia+ medullary cells in the thymocyte purged rats. All of these changes were reversible in the normal rat after cessation of CsA, with near normal recovery in 3 weeks. No morphologic or immunopathologic changes were noted in the cortical thymocytes. These cells did, however, acquire CsA receptors, as detected by the binding of fluorescent dansylated CsA.
已知环孢素A（CsA）会使胸腺体积减小，尤其是胸腺髓质。目前尚不清楚这些变化的意义。本研究揭示了CsA（15毫克/千克/天）诱导的胸腺髓质的几种免疫病理变化。胸腺的重量和相对大小急剧且迅速地萎缩，在1周内观察到明显变化。髓质胸腺细胞表现出与对照大鼠中所见的大鼠T细胞表型分离，但此类细胞的数量根据髓质残余物明显减少。这与胸腺细胞的成熟停滞一致。在处死前2天对对照或CsA处理的大鼠进行照射，直接评估髓质上皮。在CsA处理的大鼠中，哈氏小体的上皮基本缺失，而在对照大鼠中则很突出。皮质上皮细胞得以保留。用抗OX4抗体对Ia抗原进行染色显示，皮质上皮的表达变化不大，但在胸腺细胞清除的大鼠中，Ia +髓质细胞明显减少。在正常大鼠中停止使用CsA后，所有这些变化都是可逆的，3周内恢复接近正常。在皮质胸腺细胞中未观察到形态学或免疫病理学变化。然而，通过荧光丹磺酰化CsA的结合检测到，这些细胞确实获得了CsA受体。
