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 thy mus atrophy results from a depletion of small CD4(+)CD8(+) thymocytes which is caused by a diminished production of immature CD4(-)CD8(+) an d CD4(+)CD8(+) thymoblasts. 3 DBTC inhibits the activation, but not th e 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 thym ic epithelial cells. 5 DBTC enhances the Ca2+ release elicited by cros slinking of the T eel receptor complex (TcR alpha beta-CD3) on thymocy tes and moreover delays cap formation of the TcR alpha beta-CD3 recept or. 6 It is concluded that DBTC possibly interferes with the functioni ng of the cytoskeleton, The relation of the in vitro findings to the i nhibition of immature CD4(-)CD8(+) thymocyte activation and the induct ion of thymus atrophy is unknown as yet.