Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
Regeneration of the thymus was studied in rats that were treated with a single oral dose of the organotin compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.
Pieters
R H
RH
Research Institute of Toxicology, University of Utrecht, The Netherlands.
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Lam
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Seinen
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Bloksma
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Penninks
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D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001284:Atrophy / Q000139:chemically induced; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D008297:Male; D009947:Organotin Compounds; D051381:Rats; D017208:Rats, Wistar; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis*; D012038:Regeneration / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000473:pathology / Q000502:physiology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D009947:Organotin Compounds; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; C020735:dibutyldichlorotin