The cell cycle block and lysis of an activated T cell hybridoma are distinct processes with different Ca2+ requirements and sensitivity to cyclosporine A.
Open Access
- 1 June 1989
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 142 (11) , 4085-4092
- https://doi.org/10.4049/jimmunol.142.11.4085
Abstract
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.This publication has 10 references indexed in Scilit:
- Thy-1- and Ly-6-mediated lymphokine production and growth inhibition of a T cell hybridoma require co-expression of the T cell antigen receptor complex.The Journal of Immunology, 1988
- Aluminum fluoride induces phosphatidylinositol turnover, elevation of cytoplasmic free calcium, and phosphorylation of the T cell antigen receptor in murine T cells.The Journal of Immunology, 1987
- The cyclosporins inhibit lymphocyte activation at more than one site.The Journal of Immunology, 1987
- Antigen activation of murine T cells induces tyrosine phosphorylation of a polypeptide associated with the T cell antigen receptorCell, 1986
- Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium.Proceedings of the National Academy of Sciences, 1984
- Permissive role of calcium in the inhibition of T cell mitogenesis by calmodulin antagonists.The Journal of Immunology, 1983
- Calcium‐dependent activation of lymphocytes by ionophore, A23187, and a phorbol ester tumor promoterJournal of Cellular Physiology, 1983
- Interaction of calcium antagonists with cyclic AMP phosphodiesterases and calmodulinBiochemical and Biophysical Research Communications, 1982
- Calmodulin Plays a Pivotal Role in Cellular RegulationScience, 1980
- Monoclonal cytolytic T-cell lines.The Journal of Experimental Medicine, 1979