Organotin-induced thymus atrophy concerns the OX-44+ immature thymocytes. Relation to the interaction between early thymocytes and thymic epithelial cells?
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.
Pieters
R H
RH
Division Immunotoxicology, University of Utrecht, The Netherlands.
Kampinga
J
J
Bol-Schoenmakers
M
M
Lam
B W
BW
Penninks
A H
AH
Seinen
W
W
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002450:Cell Communication / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009947:Organotin Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D009947:Organotin Compounds; C020735:dibutyldichlorotin