Rethinking Thymic Tolerance: Lessons from Mice. Issue 4 (April 2019)

• Record Type: Journal Article
• Authors: Inglesfield, Sarah; Cosway, Emilie J.; Jenkinson, William E.; Anderson, Graham
• Is Part Of: Trends in immunology. Volume 40:Issue 4(2019)
• Page Start: 279
• Page End: 291
• Publication Date: 2019-04
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2019.01.011
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : In the thymus, distinct cortex and medulla areas emphasize the division of labor in selection events shaping the αβT cell receptor repertoire. For example, MHC restriction via positive selection is a unique property of epithelial cells in the thymic cortex. Far less clear are the events controlling tolerance induction in the medulla. By acting in concert through multiple roles, including antigen production/presentation and chemokine-mediated control of migration, we propose that medullary epithelium and dendritic cells collectively enable the medulla to balance T cell production with negative selection and Foxp3 + regulatory T cell (Treg) development. We examine here the features of these medullary resident cells and their roles in T cell tolerance, and discuss how imbalance in the thymus can result in loss of T cell tolerance. Highlights: Foxp3 + Treg development and negative selection in the thymus remain key components of T cell tolerance mechanisms, both of which are controlled by the thymic medulla. Medulla dysgenesis does not necessarily predispose to a loss of T cell tolerance, arguing that thymic medulla function can be preserved despite limitations in the availability of medullary thymic epithelial cells (mTECs). Recently identified heterogeneity within the thymic stroma suggests that multiple subsets of mTECs play active roles in imposing T cell tolerance. Accurate examination of the rates and mechanisms controlling Foxp3 + Treg selection in the thymus must take into account the presence of peripheral recirculating cells within the Foxp3 + intrathymic Treg pool.