The contribution of chemokines and migration to the induction of central tolerance in the thymus

Zicheng Hu, Jessica Naomi Lancaster, Lauren I.R. Ehrlich

Research output: Contribution to journalShort surveypeer-review

17 Scopus citations

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 autoreactive 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.

Original languageEnglish (US)
Article number398
JournalFrontiers in immunology
Volume6
Issue numberJUL
DOIs
StatePublished - 2015

Keywords

  • Central tolerance
  • Chemokine receptors
  • Negative selection
  • Thymocyte migration
  • Thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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