Molecular and Cellular Events of T Cell Development

Although some T cell differentiation can occur outside the thymus, by far majority of the T cells develop within the thymus, and this chapter discusses the intrathymic differentiation. A major turning point in this field came with the identification of the surface receptors used by T cells to recognize and respond to foreign antigens in association with the products of major histocompatibility complex (MHC). Based on the understanding of the molecular basis, T cell development can be divded into three stages: early genetic events leading to T cell receptor (TCR) expression, cellular selection, and acquisition of mature effector function. Analysis of the T cell development in the adult thymus has been greatly facilitated by the fact that thymocyte subsets can be separated, on the basis of surface markers, into relatively homogeneous populations that represent defined developmental stages. Some of these populations correspond closely to early fetal thymocytes but are present in much smaller proportion. There is an astounding evolutionary conservation in thymocyte ontogeny and subset distribution ranging from chicken to human. Although the time line is based on murine fetal ontogeny, the temporal and lineage relationships appear to be evolutionarily conserved. As with most scientific work, the recent elucidation of lineage pathways and of selection mechanisms involved in T cell development has posed new questions and opened new frontiers. The lineage map provided in the chapter represents a summary of the events, for which there is now reasonable consensus, based on multiple experimental approaches.