In the present study the susceptibility of different subsets of immatu
re rat thymocytes to undergo apoptosis was examined, Unfractionated ra
t thymocytes were negatively enriched into immature double positive (C
D4(+)CD8(+)), immature single positive (CD4(-)CD8(+)CD3(-)) and triple
negative (CD4(-)CD8(-)CD3(-)) thymocytes. These enriched subsets of i
mmature thymocytes were then exposed to various apoptotic stimuli such
as dexamethasone, etoposide and thapsigargin which readily induced ap
optosis in unfractionated rat thymocytes. We found that the double pos
itive thymocytes and their precursor cells, i.e. the single positive i
mmature thymocytes, were equally sensitive to apoptosis after treatmen
t,vith the apoptotic stimuli, In sharp contrast, the early migrants or
precursor-containing thymocytes which are triple negative have a lowe
r spontaneous apoptosis rate and were relatively resistant to all the
apoptotic stimuli. These findings showed a breakpoint in thymocyte sen
sitivity to apoptosis which occurs after the onset of CD8 expression,
suggesting that susceptibility of thymocytes to apoptosis is developme
ntally regulated. (C) 1997 Federation of European Biochemical Societie
s.