cAMP inhibits the OKT3-induced increase in cytoplasmic free calcium in the Jurkat T cell line: the degree of inhibition correlates inversely with the amount of CD3 binding ligand used.
We have investigated the effect of cAMP concentration on the CD3-mediated rise in intracellular Ca2+ induced by anti-CD3 monoclonal antibody in the human T cell leukemia line Jurkat. Forskolin, prostaglandin E2 (PGE2) and dibutyryl cAMP (db-cAMP) were used to increase intracellular cAMP concentrations. Treatment of Jurkat cells with forskolin or db-cAMP for 3 h inhibited the subsequent rise in intracellular Ca2+ concentration induced by an optimally mitogenic dose of 100 ng/ml of the anti-CD3 OKT3, whereas PGE2 counteracted the Ca2+ rise only marginally. The inhibitory effect of forskolin and PGE2 on the Ca2+ signal correlated with their abilities to induce increased cAMP levels in Jurkat cells. The suppression of the Ca2+ response was dependent on the concentration of the cAMP-elevating agent and the time of pre-incubation with the drug. The cAMP-mediated inhibition of the Ca2+ response diminished or disappeared when increasing concentrations of OKT3 were used to stimulate the rise in intracellular Ca2+ concentration. The results indicate that cAMP participates in the regulation of T lymphocyte activation at the level of signal transduction. Our findings, which stress the crucial role of the concentration of the ligand used to trigger Ca2+ responses, provide an explanation to previous contradictory reports on the impact of cAMP on the signal transduction in T cells.
Papadogiannakis
N
N
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Sweden.
Nordström
T E
TE
Andersson
L C
LC
Wolff
C H
CH
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D003593:Cytoplasm / Q000032:analysis; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium