Two distinct stages in the transition from naive CD4 T cells to effecters,early antigen-dependent and late cytokine-driven expansion and differentiation

Efficient peptide presentation by professional APC to naive and effector CD 4 T cells in vitro is limited to the first 1-2 days of culture, but is none theless optimum for effector expansion and cytokine production. In fact, pr olonging Ag presentation leads to high levels of T cell death, decreased ef fector expansion, and decreased cytokine production by recovered effecters, Despite the absence of Ag presentation beyond day 2, T cell division conti nues at a constant rate throughout the 4-day culture. The Ag-independent la ter stage depends on the presence of IL-2, and we conclude optimum effector generation depends on an initial 2 days of TCR stimulation followed by an additional 2 days of Ag-independent, cytokine driven T cell expansion and d ifferentiation.