A FUNCTIONALLY COMPROMISED INTERMEDIATE IN EXTRATHYMIC CD8(-CELL DELETION() T)

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.