The organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+ thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta-/low CD2high thymoblast subset.
Thymic changes in the rat induced by the thymus atrophy-inducing organotin compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8- and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44- cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells, representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When compared to controls, the FSChigh cell population of DBTC-treated rats contained less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T-cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+ cells, representing mature CD4+ cells, were not affected. These data indicate that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR alpha beta-low thymoblasts. This initial event may result in a decreased formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These characteristics of the initially depleted subset indicate a specific anti-proliferative effect of DBTC and may give clues for the mechanism involved in the induction of thymus atrophy.
Research Institute of Toxicology, University of Utrecht, The Netherlands.
R H
RH
Pieters
M
M
Bol
B W
BW
Lam
W
W
Seinen
A H
AH
Penninks
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001284:Atrophy / Q000276:immunology; D018801:CD2 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D016827:CD8 Antigens / Q000032:analysis; D008297:Male; D009947:Organotin Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis; D011990:Receptors, Transferrin; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; C068126:CD71 antigen; D016827:CD8 Antigens; D009947:Organotin Compounds; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011990:Receptors, Transferrin; C020735:dibutyldichlorotin