Ca2+ response in single human T cells induced by stimulation of CD4 or CD8 and interference with CD3 stimulation

Abstract A Ca 2+ imaging method has been used to demonstrate simultaneously the magnitude and time course of the increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in 10–30 individual human peripheral T cells following stimulation by anti-CD4 or anti-CD8 monoclonal antibody (MAb) as well as anti-CD3 MAb. The rise in [Ca 2+ ] i began within 10 s of the introduction of the MAb and reached a peak of 240 nM (mean of 73 cells) in 20–40 s. The peak was followed by a slow decrease persisting for 6–8 min. Comparing Ca 2+ responses in the presence and absence of external Ca 2+ , the rise in [Ca 2+ ] i was found to be caused by both transient intracellular Ca 2+ release and a long-lasting Ca 2+ influx from outside the cell. Cross-linking of CD4 or CD8 using anti-IgG antibody augmented the response in individual cells, as seen in the higher peak (365–390 nM) and the longer duration (over 10 min). Simultaneous stimulation of CD3 and CD4 did not cause a summation of Ca 2+ responses but caused a suppression in the CD3-mediated Ca 2+ response. The results support the view that CD4 and CD8 play a role in signal transduction for T cell activation and that the CD4-derived signal interferes with the CD3-derived signal at some stage in the signalling pathway causing the Ca 2+ response.