We have established a model system for analyzing the induction of self
-tolerance among mature peripheral T cells in V beta 5 TCR Tg mice. Bo
th CD4(+)V beta 5(+) and CD8(+)V beta 5(+) cells undergo a superantige
n-driven chronic deletion in the periphery of I-E(-) mice. Prior to th
eir disappearance, CD4(+) transgene-expressing cells are activated and
then rendered anergic to further stimulation through their TCRs. This
scenario differs strikingly in the CD8(+) cellular compartment, which
is characterized by a distinct population of CD8(lo)V beta 5(lo) cell
s localized to the blood and spleen. CD8(lo) cells are small, express
the surface phenotype of memory cells, and rapidly incorporate BrdU in
vive. The kinetics of their appearance and disappearance in adult thy
mectomized mice, the rapid chasing of BrdU from labeled cells, and the
ir in vivo cortisone sensitivity all suggest CD8(lo) cells are slated
for deletion. Furthermore, their functional incompetence can be docume
nted in vitro in the absence of internucleosomal DNA fragmentation. Th
us, we have identified an intermediate population of T cells targeted
for peripheral deletion that, although functionally compromised, has n
ot yet undergone programmed cell death.