Ej. Dewaal et al., ALTERATIONS OF DENDRITIC CELLS IN THE RAT THYMUS WITHOUT EPITHELIAL-CELL LOSS DURING CYCLOSPORINE TREATMENT AND RECOVERY, Toxicology, 110(1-3), 1996, pp. 133-151
After cyclosporine treatment, dendritic cells disappear from the rat t
hymic medulla, The present study was undertaken to examine the ultrast
ructural alterations in the dendritic cell population during 14-day cy
closporine treatment and subsequent 6-week recovery, Four dendritic ce
ll subtypes were defined ultrastructurally by a newly developed classi
fication system, In addition, the potential effect of cyclosporine on
six medullary epithelial cell subtypes was studied. During cyclosporin
e treatment, a prominent reduction of dendritic cells was seen at the
ultrastructural level, whereas the total number of medullary epithelia
l cells remained largely unchanged, These findings were confirmed by i
mmunohistochemistry. The number of mature dendritic cells declined lat
er than the number of immature ones, A decrease in the antigen-process
ing capacity of remaining dendritic cells was suggested by the disappe
arance of Birbeck granules and the reduced number of tubulovesicular c
omplexes. These findings support a disturbance of clonal deletion duri
ng cyclosporine treatment, The dendritic cell alterations appeared rev
ersible 4 weeks after the restoration of the original architecture. Du
ring recovery, dendritic cells displaying lysosomal elements outnumber
ed those found in the normal uninvoluted thymus, This phenomenon proba
bly reflects an enhanced turnover of cell organelles. No treatment-rel
ated effect on epithelial cell subtypes was seen.