Immune Netw.  2015 Jun;15(3):111-120. 10.4110/in.2015.15.3.111.

The Role of Dendritic Cells in Central Tolerance

• Oh J
• Shin JS

• KMID: 2168036
• DOI: http://doi.org/10.4110/in.2015.15.3.111

Abstract

Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.

Keyword

Dendritic cell; Central tolerance; Thymus; Clonal deletion; Negative selection; Regulatory T cell

MeSH Terms

Autoantigens
Blood Vessels
Central Tolerance*
Clonal Deletion
Dendritic Cells*
Epithelial Cells
T-Lymphocytes
T-Lymphocytes, Regulatory
Thymocytes
Thymus Gland
Autoantigens

Figure

• 

  Figure 1 The role of dendritic cells in the thymus. DCs are positioned in the medullary region of the thymus, and acquire tissue-restricted antigens from mTECs (A) and circulating antigens from blood vessels (B). Some thymic DCs originate from periphery carrying antigens acquired from the peripheral tissue sites (C). The acquired antigens are presented to CD4+ thymocytes via MHCII (D) and CD8+ thymocytes via MHCI (E), and this presentation results in thymocyte apoptosis or Treg cell differentiation (F and G).

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