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, most of the studies used potentially toxic pharmacological agents for cell cycle 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 Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0-G1, S, and G2-M phases of the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca(2+) flux, cytolytic recognition 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 certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell cycle.
Karas
M
M
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1770, USA. karas@box-k.nih.gov
Zaks
T Z
TZ
Liu
J L
JL
LeRoith
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D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D053222:Fas Ligand Protein; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D002118:Calcium