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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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The ICOS-ICOSL pathway tunes thymic selection.

Mengqi Dong1,2, Jinsam Chang3,4, Marie-Ève Lebel2

  • 1Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada.

Immunology and Cell Biology
|December 28, 2021
PubMed
Summary

Inducible T-cell costimulator (ICOS) and its ligand (ICOSL) are expressed in the thymus. ICOS signaling fine-tunes T-cell receptor signals, contributing to self-tolerance during T-cell development.

Keywords:
ICOSICOSLnegative selectionthymic antigen-presenting cellsthymocytes

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Area of Science:

  • Immunology
  • T-cell biology
  • Central tolerance

Background:

  • Negative selection of developing T cells is crucial for self-tolerance.
  • Thymic antigen-presenting cells (APCs) mediate negative selection via self-antigens and costimulatory molecules.
  • Inducible T-cell costimulator (ICOS) is a CD28 family costimulatory molecule, but its role in central tolerance is unclear.

Purpose of the Study:

  • To investigate the expression of ICOS ligand (ICOSL) in the thymus.
  • To determine the role of ICOS signaling in thymic T-cell selection and central tolerance.

Main Methods:

  • Immunohistochemistry to detect ICOSL expression in thymic cells.
  • Flow cytometry to analyze ICOS expression on developing T cells.
  • Assessment of T-cell receptor signal strength during thymic selection.

Main Results:

  • ICOSL is expressed by thymic dendritic cells, medullary thymic epithelial cells, and B cells.
  • ICOS expression increases with T-cell maturation in the thymus.
  • ICOS expression correlates with T-cell receptor signal strength during thymic selection.
  • Evidence suggests ICOS signaling mediates negative selection.

Conclusions:

  • ICOSL is present in the thymus and expressed by various APC subsets.
  • ICOS signaling appears to modulate T-cell receptor signals during thymic selection.
  • ICOS plays a role in fine-tuning T-cell selection, contributing to the generation of a tolerant T-cell repertoire.