Organotin-induced thymus atrophy concerns the OX-44+ immature thymocytes. Relation to the interaction between early thymocytes and thymic epithelial cells?

Abstract

After single oral application of the organotin compound di-n-butyltindichloride (DBTC) to rats, a reversible dose-dependent thymus weight reduction is observed. This is maximal at day 4 and recovers to the control value approximately at day 9 after administration. In this study the changes in thymocyte subpopulations after a single oral dose of 15 mg DBTC/kg body weight were analysed by immunohistology. Thymus glands of exposed rats were collected at day 1,2,3,4,5,7 and 9 after DBTC dosing and frozen sections were screened for various thymocyte differentiation antigens. Staining by mAb HIS-44 that labels a subset of cortical thymocytes showed that the thymus atrophy was restricted to the cortex. Here a time-dependent decrease of labelling by CD2 (OX-34), CD8 (OX-8), CD4 (ER-2), and CD5 (OX-19) was observed. In contrast, the number of cortical OX-44+ cells increased from day 2 to day 5. This increase can reflect an increase of CD4-CD8- double-negative thymocytes or of macrophages. However, most of these OX-44+ cells were negative for acid phosphatase, which is present in most macrophages. We concluded that these OX-44+ cells were mainly CD4-CD8- thymocytes and that the thymocyte subpopulation of this phenotype, i.e. CD4-CD8-OX-44+, may be the target cell for DBTC. It is discussed whether DBTC might disturb the interaction of early thymocytes and thymic epithelium, probably by an interaction with the CD2 antigen.