Alterations of dendritic cells in the rat thymus without epithelial cell loss during cyclosporine treatment and recovery.
After cyclosporine treatment, dendritic cells disappear from the rat thymic medulla. The present study was undertaken to examine the ultrastructural alterations in the dendritic cell population during 14-day cyclosporine treatment and subsequent 6-week recovery. Four dendritic cell subtypes were defined ultrastructurally by a newly developed classification system. In addition, the potential effect of cyclosporine on six medullary epithelial cell subtypes was studied. During cyclosporine treatment, a prominent reduction of dendritic cells was seen at the ultrastructural level, whereas the total number of medullary epithelial cells remained largely unchanged. These findings were confirmed by immunohistochemistry. The number of mature dendritic cells declined later than the number of immature ones. A decrease in the antigen-processing capacity of remaining dendritic cells was suggested by the disappearance of Birbeck granules and the reduced number of tubulovesicular complexes. These findings support a disturbance of clonal deletion during cyclosporine treatment. The dendritic cell alterations appeared reversible 4 weeks after the restoration of the original architecture. During recovery, dendritic cells displaying lysosomal elements outnumbered those found in the normal uninvoluted thymus. This phenomenon probably reflects an enhanced turnover of cell organelles. No treatment-related effect on epithelial cell subtypes was seen.
De Waal
E J
EJ
National Institute of Public Health and The Environment, Bilthoven, The Netherlands.
Rademakers
L H
LH
Schuurman
H J
HJ
Vos
J G
JG
Van Loveren
H
H
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005629:Frozen Sections; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D007275:Injections, Intravenous; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine