THE DURATION OF ANTIGENIC-STIMULATION DETERMINES THE FATE OF NAIVE AND EFFECTOR T-CELLS

It is known that T cells engage antigen-presenting cells (APCs) in a s table interaction that results in sustained TCR signaling. We show her e that the duration of this process is critical in determining whether T cells will be activated or deleted. Whereas naive T cells require a pproximately 20 hr of sustained signaling to be committed to prolifera tion, effector T cells become committed after only 1 hr but die follow ing activation if antigenic stimulation is prolonged. Costimulation by anti-CD28 facilitates T cell activation by decreasing the time of com mitment and by protecting T cells from death. These findings explain i n quantitative terms the essential requirement for professional APCs i n T cell priming and show that the duration of antigenic stimulation i s the major factor determining the fate of naive and effector T cells.