A survival guide to early T cell development

The survival of immature T cell precursors is dependent on both thymus-derived extrinsic signals and self-autonomous pre-TCR-mediated signals. While the role of cytokines and the pre-TCR in promoting thymocyte survival has been well established, the relationship between pro- and anti-apoptotic signaling cascades remains poorly defined. Recent studies have established a link between cell survival and growth factor-mediated maintenance of cellular metabolism. In this regard, the Notch signaling pathway has emerged as more than an inducer of T lineage commitment and differentiation, but also as a potent trophic factor, promoting the survival and metabolic state of pre-T cells. In this review, we describe current concepts of the intracellular signaling pathways downstream of cell intrinsic and extrinsic factors that dictate survival versus death outcomes during early T cell development.