The thymus atrophy-inducing organotin compound DBTC inhibits the binding of thymocytes to thymic epithelial cells

Int J Immunopharmacol. 1995 Apr;17(4):329-37. doi: 10.1016/0192-0561(94)00103-u.

Abstract

In this study, it is examined whether the organotin compound di-n-butyltindichloride (DBTC), which has been shown to inhibit immature thymocyte proliferation, is able to disturb the binding between thymocytes and thymic epithelial cells (TEC). To that end, an enzyme-linked binding assay was developed in which the amount of binding of Thy-1+ (mAb ER4)-thymocytes to the rat-derived TEC-line IT45R1 (IT45R1-TEC) could be detected. It was found that preincubation of thymocytes with 3-5 microM DBTC for 30 min inhibited the binding by 50-60% during a 1 h adhesion period. By extending the preincubation period to 1 h and the adhesion period to 22 h, 0.1 microM DBTC was already sufficient to reduce the binding with 60-80%. Further characterization of the binding revealed that splenic lymphocytes were unable to bind to the MHC class II-negative IT45R1-TEC. Since dextran sulfate inhibited the binding as well, sulfated polysaccharide-binding molecules such as Thy-1 and CD2 are likely to be involved in the binding. Electron microscopy showed filament-containing microvilli at the site of interaction. The results are discussed in relation to the mechanism of DBTC-induced thymus atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy
  • CD2 Antigens / metabolism
  • Cell Adhesion / drug effects
  • Cell Line
  • Depression, Chemical
  • Dextran Sulfate / pharmacology
  • Epithelium / metabolism
  • Epithelium / ultrastructure
  • Histocompatibility Antigens Class II / immunology
  • Microscopy, Electron
  • Organotin Compounds / pharmacology*
  • Organotin Compounds / toxicity
  • Rats
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / metabolism
  • Thy-1 Antigens / metabolism
  • Thymus Gland / drug effects*
  • Thymus Gland / pathology

Substances

  • CD2 Antigens
  • Histocompatibility Antigens Class II
  • Organotin Compounds
  • Thy-1 Antigens
  • Dextran Sulfate
  • dibutyldichlorotin