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

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. Both CD4(+)V beta 5(+) and CD8(+)V beta 5(+) cells undergo a superantigen-driven chronic deletion in the periphery of I-E(-) mice. Prior to their 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) cells 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 thymectomized mice, the rapid chasing of BrdU from labeled cells, and their in vivo cortisone sensitivity all suggest CD8(lo) cells are slated for deletion. Furthermore, their functional incompetence can be documented in vitro in the absence of internucleosomal DNA fragmentation. Thus, we have identified an intermediate population of T cells targeted for peripheral deletion that, although functionally compromised, has not yet undergone programmed cell death.