CD8+ T cells in large granular lymphocyte leukemia are not defective in activation- and replication-related apoptosis.

Persistent lymphocytosis in large granular lymphocyte leukemia (LGL) may result from defects in activation- or Fas crosslinking-induced cell death. Here we show that Fas crosslinking and CD3 activation causes apoptosis of in vitro activated CD8 T cells, but not of freshly isolated CD8 T cells. Death was partially blocked by a neutralizing antibody to FasL. Inhibition of metalloproteinase-mediated FasL solubilization significantly potentiated induction of cell death. Furthermore, CD3 plus CD28 stimulation resulted in telomeric erosion in LGL cells, and ultimately proliferation ceased. Together, these data indicate that activation- and proliferation-related cell death mechanisms are functional in LGL cells.