ABSTRACT
Introduction 156 Overview of T cell development 156 Major phenotypic markers of T cell development 156 T cell receptor gene rearrangements 158 Overview of functional events in intrathymic 159
T cell development Anatomic correlates of T cell development 159 Thymus structure and ontogeny 159 Thymic epithelial cells 160 Key events in intrathymic T cell development 162
Lineage commitment in early thymocyte precursors 162 αβ/γδ T-lineage commitment 164 β-Selection 165 Positive and negative selection 166 CD4/CD8 lineage commitment 169 Natural killer cell development 172 Conclusion 174 Key points 175 References 175
T cell development is a complex process that encompasses fundamental concepts in immunology and developmental biology. The inherent complexity in T cell development relates in large part to the strict requirements of T cells in the elicitation of diverse yet specific immune responses that protect the host organism while at the same time avoiding indiscriminate attack against itself in the form of autoimmunity. As such, T cell development is replete with decisions regarding cell differentiation, survival, and death. T cell development is a critical area of research not only because of the insights into immunology, developmental biology, and cell biology, but also because of the clinical implications of T cell biology in the context of T cell neoplasms, immune homeostasis, and immune reconstitution in the setting of immunodeficient states including human immunodeficiency virus (HIV) infection, cancer, and immunodepleting therapies including chemotherapy and hematopoietic stem cell transplantation (HSCT). In addition to T cells, natural killer (NK) and NK-T cells (whose development is not discussed in this chapter) have emerged as important contributors in immune responses to pathogens and tumors for which insights into developmental programs are currently being characterized.
