Cellular and molecular aspects of organotin-induced thymus atrophy

1. Organotin compounds, di-n-butyltin dichloride (DBTC) in particular, have been shown to cause thymus atrophy in the rat. 2. DBTC-induced thymus atrophy results from a depletion of small CD4+CD8+ thymocytes which is caused by a diminished production of immature CD4-CD8+ and CD4+CD8+ thymoblasts. 3. DBTC inhibits the activation, but not the differentiation of immature CD4-CD8+ thymocytes in vitro and in vivo suggesting a selective antiproliferative activity of DBTC. 4. DBTC inhibits the adhesion molecule-mediated binding of thymocytes to thymic epithelial cells. 5. DBTC enhances the Ca2+ release elicited by cross-linking of the T cell receptor complex (TcR alpha beta-CD3) on thymocytes and moreover delays cap formation of the TcR alpha beta-CD3 receptor. 6. It is concluded that DBTC possibly interferes with the functioning of the cytoskeleton. The relation of the in vitro findings to the inhibition of immature CD4-CD8+ thymocyte activation and the induction of thymus atrophy is unknown as yet.