Regulation of T Cell Activation and Anergy by the Intensity of the Ca²⁺ Signal in Cooperation with Other Signals

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The results of our previous in vitro study indicated that the intensity of the Ca²⁺ signal could determine T cell activation and anergy. We show here that the T cell response of mice that had been treated with cyclosporine A during oral tolerance induction was higher than that of control mice, indicating that the Ca²⁺ signal could also determine T cell activation and tolerization in vivo. However, T cell activation was not apparent at any concentration of ionomycin, although a low dose of anti-CD3 monoclonal antibody (mAb) induced activation, while a high dose induced anergy in vitro. These results indicate that the balance between the Ca²⁺ signal and other signals which can also be induced by anti-CD3 stimulation, but not the actual intensity of the Ca²⁺ signal or the presence of co-stimulation, played an important role in regulating T cell activation and anergy.