Trafficking to the Thymus Shirley L. Zhang and Avinash Bhandoola Abstract The continuous production of T lymphocytes requires that hematopoi- etic progenitors developing in the bone marrow migrate to the thymus. Rare progenitors egress from the bone marrow into the circulation, then traffic via the blood to the thymus. It is now evident that thymic settling is tightly regulated by selectin ligands, chemokine receptors, and integrins, among other factors. Identi- fication of these signals has enabled progress in identifying specific populations of hematopoietic progenitors that can settle the thymus. Understanding the nature of progenitor cells and the molecular mechanisms involved in thymic settling may allow for therapeutic manipulation of this process, and improve regeneration of the T lineage in patients with impaired T cell numbers. Contents 1 Introduction.............................................................................................................................. 2 Candidate Thymic Settling Progenitors .................................................................................. 3 Mobilization into the Circulation ........................................................................................... 4 Entering the Thymus ............................................................................................................... 4.1 The Molecular Basis of Homing.................................................................................... 4.2 The Thymic Settling Progenitor Niche.......................................................................... 5 Fetal Versus Adult Thymic Settling ....................................................................................... 6 Evolution of the Thymus and Homing................................................................................... S. L. Zhang Á A. Bhandoola (&) Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 264 John Morgan Building 3620 Hamilton Walk, Philadelphia, PA, USA e-mail: bhandooa@mail.med.upenn.edu Current Topics in Microbiology and Immunology DOI: 10.1007/82_2013_324 Ó Springer-Verlag Berlin Heidelberg 2013