AUTHOR=Hu Zicheng , Lancaster Jessica Naomi , Ehrlich Lauren I. R. TITLE=The Contribution of Chemokines and Migration to the Induction of Central Tolerance in the Thymus JOURNAL=Frontiers in Immunology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2015.00398 DOI=10.3389/fimmu.2015.00398 ISSN=1664-3224 ABSTRACT=

As T cells develop, they migrate throughout the thymus where they undergo essential bi-directional signaling with stromal cells in distinct thymic microenvironments. Immature thymocyte progenitors are located in the thymic cortex. Following T cell receptor expression and positive selection, thymocytes undergo a dramatic transition: they become rapidly motile and relocate to the thymic medulla. Antigen-presenting cells (APCs) within the cortex and medulla display peptides derived from a wide array of self-proteins, which promote thymocyte self-tolerance. If a thymocyte is auto-reactive against such antigens, it undergoes either negative selection, via apoptosis, or differentiation into the regulatory T cell lineage. This induction of central tolerance is critical for prevention of autoimmunity. Chemokines and adhesion molecules play an essential role in tolerance induction, as they promote migration of developing thymocytes through the different thymic microenvironments and enhance interactions with APCs displaying self-antigens. Herein, we review the contribution of chemokines and other regulators of thymocyte localization and motility to T cell development, with a focus on their contribution to the induction of central tolerance.