Pieters R H, Bol M, Lam B W, Seinen W, Penninks A H
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Immunology. 1992 Jun;76(2):203-8.
Thymic changes in the rat induced by the thymus atrophy-inducing organotin compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy.
使用荧光激活细胞分选术（FACS）分析，研究了胸腺萎缩诱导性有机锡化合物二正丁基二氯化锡（DBTC）诱导的大鼠胸腺变化。从第2天起，DBTC处理使CD4⁺CD8⁺胸腺细胞数量减少，并在给药后第4天和第5天达到最低水平。在这些天里，CD4⁻CD8⁻以及CD4⁻CD8⁺和CD4⁺CD8⁻亚群均未受影响。在第2天，我们观察到转铁蛋白受体（CD71）阳性的CD4⁻OX44⁻细胞（代表循环中的未成熟CD4⁻CD8⁺细胞）和CD71⁺OX44⁻细胞（代表循环中的CD4⁺CD8⁺细胞）的比例降低，但CD71⁺CD4⁻CD8⁻细胞的比例未降低。与对照组相比，DBTC处理的大鼠中FSChigh细胞群体中CD4⁻OX44⁻和OX44⁻细胞较少，这些细胞进一步被鉴定为CD2high和低T细胞受体（TcR）αβ。此外，在DBTC处理的大鼠的OX44⁻胸腺母细胞亚群中检测到的TcRαβ高细胞较少。CD4⁻CD8⁻胸腺母细胞数量似乎略有减少，而代表成熟CD4⁺细胞的CD4⁺OX44⁺细胞数量未受影响。这些数据表明，DBTC导致未成熟的CD4⁻CD8⁺CD2high TcRαβ低胸腺母细胞优先初步耗竭。这一初始事件可能导致CD4⁺CD8⁺胸腺母细胞和小CD4⁺CD8⁺胸腺细胞形成减少。最初耗竭亚群的这些特征表明DBTC具有特定的抗增殖作用，并可能为胸腺萎缩诱导机制提供线索。
