Hiramine C, Nakagawa T, Miyauchi A, Hojo K
Department of Immunology and Immunopathology, Kagawa Medical School, Japan.
Lab Invest. 1996 Aug;75(2):185-201.
Structural changes in the thymus of BALB/c mice after the intraperitoneal injection with a single high dose (200 mg/kg) of cyclophosphamide (CY) were examined. A large number of thymic nurse cell (TNC)-like structures that contained apoptotic thymocytes were observed in the thymus between 8 and 20 hours after CY treatment, just before a marked reduction in the number and proportion of PNAhi, CD3-, CD4+ CD8+ thymocytes. The majority of apoptotic thymocyte-containing TNC-like structures had an epithelial nature and were mainly located in the subcapsular and outer cortex, perivascular area of the cortex, corticomedullary junction and, in part, in the medulla. Most thymocytes seemed to undergo apoptosis synchronously in every TNC-like structure, but one or two fully intact mature thymocytes were found in every one. By 24 hours after CY treatment, many vacuoles that contained apoptotic cells in various stages of degeneration were observed within the epithelium, and most of the apoptotic cells disappeared at 24 hours. We herein demonstrated that the epithelium of TNC-like structures had a phagocytic activity in the digestion of apoptotic thymocytes by the presence of phagolysosomes with acid phosphatase activity. The epithelium left very small vacuoles with a small amount of nondigestible dense granules. The minority of apoptotic thymocyte-containing TNC-like structures scattered in the entire cortex between 8 and 20 hours after CY treatment was macrophage (M phi)-derived. Many apoptotic cell-containing M phi were observed as early as 4 hours after the CY injection. Apoptotic thymocytes of CY-treated mice showed the internucleosomal DNA fragmentation. In conclusion, CY accelerates physiologic thymocyte apoptosis, and epithelial TNC are one of the principal sites of thymocyte apoptosis as well as an environment for the nursing of immature thymocytes. Both the epithelium of TNC and M phi participate in digestion of apoptotic cells and have the efficient capacity of clearance of apoptotic thymocytes in the normal thymus at a presumed high rate.
研究了腹腔注射单次高剂量（200mg/kg）环磷酰胺（CY）后BALB/c小鼠胸腺的结构变化。在CY处理后8至20小时之间，即在PNAhi、CD3-、CD4+CD8+胸腺细胞数量和比例显著减少之前，在胸腺中观察到大量含有凋亡胸腺细胞的胸腺哺育细胞（TNC）样结构。大多数含有凋亡胸腺细胞的TNC样结构具有上皮性质，主要位于被膜下和外皮质、皮质的血管周围区域、皮质髓质交界处，部分位于髓质。每个TNC样结构中的大多数胸腺细胞似乎同步发生凋亡，但每个结构中都发现有一两个完全完整的成熟胸腺细胞。CY处理后24小时，上皮内可见许多含有处于不同退化阶段凋亡细胞的空泡，大多数凋亡细胞在24小时时消失。我们在此证明，通过具有酸性磷酸酶活性的吞噬溶酶体的存在，TNC样结构的上皮在凋亡胸腺细胞的消化中具有吞噬活性。上皮留下非常小的空泡，其中含有少量不可消化的致密颗粒。CY处理后8至20小时散布在整个皮质中的少数含有凋亡胸腺细胞的TNC样结构是巨噬细胞（M phi）来源的。早在CY注射后4小时就观察到许多含有凋亡细胞的M phi。CY处理小鼠的凋亡胸腺细胞显示出核小体间DNA片段化。总之，CY加速生理性胸腺细胞凋亡，上皮TNC是胸腺细胞凋亡的主要部位之一，也是未成熟胸腺细胞哺育的环境。TNC的上皮和M phi都参与凋亡细胞的消化，并具有以假定的高速度在正常胸腺中有效清除凋亡胸腺细胞的能力。
