J. C. PIERCE 
757 
at 48 to 72 hours from the time between the re- 
duction of DNA synthesis to its minimum and 
the reduction of DNA content to its minimum 
value. This is consistent with the value that 
Weissman* has observed for the lag time be- 
tween local labeling of thymocytes and their 
maximum time of migration to the periphery. If 
72 hours is the average holding time for thymo- 
cytes in the differentiating compartment, it can 
be calculated that this compartment accommo- 
dates one-fourth of the net cell production of 
the replicating compartment. This implies that 
three-quarters of the cells which were newly 
formed in the replicating compartment either 
migrated from the thymus or were destroyed 
within the thymus very soon after mitotic divi- 
sion was completed. 
Because of the lag between the time that the 
DNA of cells was labeled in the thymus and the 
appearance of these cells in peripheral tissues,^ 
most of these cells probably died in the thymus. 
The sensitivity of the replicating cells in the 
thymus to dexamethasone was remarkable. The 
rate of cell production which gave a more accu- 
rate measure of the size of the replicating pool 
than either the DNA turnover rate or the DNA 
content of the thymus was reduced to three per- 
cent of the control value one day after dexame- 
thasone. The rate of DNA loss from the thymus 
during the initial 24 hours, however, could not 
be accounted for solely by loss of the replicating 
cells and normal migration from the differen- 
tiating or small thymocyte compartment. An 
additional amount of DNA equal to approxi- 
mately twenty percent of the cells in the differ- 
entiating compartment was lost during this 
period. During the next two days the rate of 
DNA loss from the thymus was consistent with 
the normal rate of loss of cells from the differen- 
tiating compartment. This suggests that while 
thymocytes during division and immediately 
after were exquisitely sensitive to dexametha- 
sone during the additional time that these cells 
resided in the thymus prior to migration, this 
sensitivity to dexamethasone was lost. This loss 
of sensitivity to dexamethasone appears to be 
similar to the loss of alloantigens which has 
been observed during differentiation of thymus 
cells.9 
SUMMARY 
Thymus cell kinetics were studied in normal 
rats and after treatment with 0.2 mg. of dexa- 
methasone, intravenously. 
The studies are consistent with a thymus 
model with three compartments: a replicating 
cell compartment, a differentiating cell com- 
partment, and a static cell compartment. 
It was concluded that all of the cells in the rep- 
licating cell compartment and twenty percent of 
the cells in the differentiating cell compartment 
are exquisitely sensitive to dexamethasone but 
that thymocytes lose this sensitivity as they un- 
dergo further differentiation in the differen- 
tiating compartment. 
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