Naïve T cells do not proliferate in normal individuals in the absence of antigen stimulation, but they proliferate spontaneously when T cells are severely depleted. We show here that coculture of syngeneic dendritic cells (DC) with naïve T cells expressing a single T cell receptor also results in T cell proliferation in the absence of foreign antigen. As in lymphopenic mice, where T cell proliferation depends upon DC, this response in the coculture system requires interaction of the T cells' T cell receptor with self-peptide–MHCs on DC. This in vitro proliferation also requires soluble factors, including IL-15 secreted by DC, and can be inhibited potently by cell–cell contact with CD4⁺CD25⁺ regulatory T cells. The coculture system described may illuminate mechanisms that maintain stable numbers of T cells in normal individuals.