We have studied two key stages of CD4 development that serve as important checkpoints in determining whether a response will occur, how big it will be, and how long it will last, The response of naive CD4 cells is strictly regulated by the requirement for interaction of the potential precursor with an antigen-presenting cell-expressing multiple costimulatory molecules such as B7 family and intercellular adhesion molecule-1. The extent of naive cell proliferation is critically dependent on interleukin-2, whose autocrine production is similarly regulated, We show that effector CD4 cells can either die, expand, and/or generate memory, Antigen stimulation accelerates death or promotes expansion dependent on the presence of cytokines, Interleukin-2 and transforming growth factor-beta synergize to block apoptosis and favor extensive effector expansion.
