T cell homeostasis is a self-regulating process for maintaining the size of the peripheral T cell pool. Although dendritic cells (DCs) seem to be important in T cell homeostasis, the molecular regulation of DC-mediated T cell homeostasis is unknown. We show that human DCs activated by thymic stromal lymphopoietin (TSLP) induced a robust expansion of autologous CD4(+) T cell populations, which depended on self peptide-major histocompatibility complex. The proliferating T cells adopted and maintained a central memory polyclonal phenotype and could differentiate into T helper type 1 or type 2 effector cells. These results, together with findings of TSLP expression in epithelial cells of mucosal lymphoid tissues and thymus, indicate that TSLP is involved in DC-mediated CD4(+) T cell homeostasis.