As thymocytes differentiate and undergo selection in the 3 dimensional thymic milieu, they undergo obligate interactions with heterogeneous stromal cells, such as dendritic cells (DC), macrophages (MΦ), cortical thymic epithelial cells (cTEC), and medullary thymic epithelial cells (mTEC). Stromal cells deliver essential cell-bound and soluble molecular signals that promote thymocyte proliferation, differentiation, and/ or apoptosis. Reciprocally, developing thymocytes provide signals to thymic stromal cells essential for differentiation and maintenance of the stromal compartment. We seek to understand the molecular cues and cellular interactions between thymocytes and stromal cells that promote differentiation and selection of a diverse and non-autoreactive T cell pool in healthy individuals, as well as to elucidate the mechanisms of age-associated thymic involution that result in diminished T cell immunity during aging.