Thymus-Derived Signals Regulate Early T-Cell Development

T cells develop in the thymus from uncommitted progenitors under the influence of multiple soluble and membrane-associated factors that regulate the migration, survival, proliferation, and differentiation of progenitor thymocytes. The role of cytokines such as stem cell factor and IL-7 in this process is well established. However, several recent studies have demonstrated an important role for other soluble factors in T-cell development, including WNTs, bone morphogenetic proteins, and Hedgehog proteins. Other studies have clarified how chemokines regulate the migration of progenitor thymocytes at various stages of development. Furthermore, the Notch pathway has emerged as the critical inducer of T-lineage commitment and differentiation, and Notch ligands expressed by the thymic stroma likely provide essential developmental cues throughout early T-cell development. In this review, we discuss recent advances in our understanding of how thymus-derived signals regulate early T-cell development.