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 re sult from defects in activation- or Fas crosslinking-induced cell death. He re 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 me talloproteinase-mediated FasL solubilization significantly potentiated indu ction of cell death. Further-more, CD3 plus CD28 stimulation resulted in te lomeric 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. Published by Elsevier Science Ltd.