The cell cycle block and lysis of an activated T cell hybridoma are distinct processes with different Ca2+ requirements and sensitivity to cyclosporine A.
Stimulation of transformed T cells leads to both lymphokine secretion and inhibition of spontaneous growth. Studies performed with an Ag-specific T cell hybridoma demonstrated that growth inhibition is an early (within 1 h) manifestation of activation. Experiment in which extracellular Ca2+ was chelated or in which cyclosporine A was included indicated that activation-associated growth inhibition is a two-step process. The first phase is the establishment of a G1/S cell cycle block; it does not require extracellular Ca2+ and is not prevented by the addition of cyclosporine A. The second phase is cell lysis. It can be detected 4 to 6 h after activation, requires the presence of extracellular Ca2+, and is prevented when stimulation occurs in the presence of cyclosporine A. The observation that both Ca2+ depletion and cyclosporine A prevented IL-2 secretion at all time points indicates that the pathways leading to lymphokine secretion and the G1/S block diverge early in the course of the cellular response, and establish the cell cycle block as a distinct activation event with unique characteristics.
Merćep
M
M
Biological Response Modifiers Program, National Cancer Institute, Bethesda, MD 20892.
Noguchi
P D
PD
Ashwell
J D
JD
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003524:Cyclosporins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005110:Extracellular Space / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis; D007399:Interphase / Q000187:drug effects; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
D003524:Cyclosporins; D006131:Growth Inhibitors; D007376:Interleukin-2; D002118:Calcium; D013936:Thymidine