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Thymic Crosstalk: An Overview of the Complex Cellular Interactions That Control the Establishment of T-Cell Tolerance

  • Magali IrlaEmail author
Chapter

Abstract

The thymus ensures the generation of a self-tolerant T-cell repertoire capable of recognizing foreign antigens. The selection of the T-cell repertoire is dictated by the thymic microenvironment. Among stromal cells, medullary thymic epithelial cells (mTECs) play a pivotal role in this process through their unique ability to express thousands of tissue-restricted self-antigens. In turn, developing T cells control the pool and maturation of mTECs. This phenomenon of bidirectional interactions between TECs and thymocytes is referred to as thymic crosstalk. In this chapter, I discuss the discovery of thymic crosstalk and our current understanding of bidirectional interactions between mTECs and thymocytes. Finally, I summarize recent advances indicating that thymic crosstalk is not restricted to TECs and thymocytes but also occurs between TECs and dendritic cells, as well as B cells and thymocytes. This complex cellular interplay is essential for efficient T-cell selection.

Keywords

Thymic crosstalk Thymic medulla Medullary thymic epithelial cells Dendritic cells B cells Negative selection Central tolerance 

Abbreviations

Aire

Autoimmune Regulator

cDCs

Conventional dendritic cells

cTECs

Cortical thymic epithelial cells

DN

Double negative cells

DP

Double positive cells

Fezf2

Fez family zinc-finger 2

LTα

Lymphotoxin α

LTβR

Lymphotoxin beta receptor

mTECs

Medullary thymic epithelial cells

nTregs

Natural regulatory T cells

OVA

Ovalbumin

pDCs

Plasmacytoid dendritic cells

RANKL

Receptor Activator of Nuclear factor Kappa-B Ligand

SP

Single positive cells

TECs

Thymic epithelial cells

TCR

T-cell receptor

TRAs

Tissue-restricted self-antigens

WT

Wild-type

Notes

Acknowledgments

I gratefully thank Prof. Arnauld Sergé (Centre de Recherche en Cancérologie de Marseille) and Teshika Jayewickreme (Harvard University) for constructive comments. This work was supported by the Marie Curie Actions (Career Integration Grants, CIG_SIGnEPI4Tol_618541 to MI), institutional grants from Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique and Aix-Marseille Université.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Centre d’Immunologie de Marseille-Luminy (CIML), INSERM U1104, CNRS UMR7280Aix-Marseille Université UM2Marseille Cedex 09France

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