T cell receptor-induced activation and apoptosis in cycling human T cells occur throughout the cell cycle

Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, m ost of the studies used potentially toxic pharmacological agents for cell c ycle synchronization. A panel of human melanoma tumor-reactive T cell lines , a CD8 + HER-2/neu-reactive T cell clone, and the leukemic T cell line Jur kat were separated by centrifugal elutriation. Fractions enriched for the G 0-G1, S, and G2-M phases of:the cell cycle were assayed for T cell receptor -mediated activation as measured by intracellular Ca2+ flux, cytolytic reco gnition of tumor targets, and induction of Fas Ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a c ertain phase of the cell cycle, leading us to conclude that in nontransform ed human T cells, both activation and apoptosis through T cell receptor act ivation can occur in all phases of the cell-cycle.