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Thymic and Peripheral Generation of CD4+ Foxp3+ Regulatory T Cells

  • Paola Romagnoli
  • Julie Ribot
  • Julie Tellier
  • Joost P.M. van Meerwijk
Chapter

Abstract

The existence of regulatory T lymphocytes (“Treg”) was suspected more than twenty years ago from seminal experiments on induction of transplantation tolerance in chick-quail chimeras. Much more recently, naturally occurring thymus-derived Treg were characterized phenotypically and functionally. It became clear that these cells are critically involved in prevention of autoimmune disease and, accordingly, it was found that the Treg repertoire is enriched in autospecific cells. The latter observation incited substantial work on selection and thymic lineage commitment of Treg. Some results supported an “instructive” model for Treg commitment in which precursors expressing a TCR with high affinity for self-ligands are directed to the Treg lineage. Other evidence supported a “stochastic” model in which commitment to the Treg lineage occurs independently of TCR specificity. The autospecific Treg-repertoire appears to be shaped in the thymus through a two-step positive selection process, one step occurring in the thymic cortex and the other in the medulla, combined with reduced sensitivity to negative selection. Also peripheral and therefore fully mature conventional T cells can, under certain experimental conditions, be converted to the Treg lineage and thus contribute to establishing tolerance to innocuous, e.g. intestinal, antigens. Understanding the thymic and peripheral mechanisms of Treg-induction will contribute to development of therapies involving modulation of these cells in pathologies ranging from cancer, via autoimmunity, to graft-rejection and Graft-versus-host disease.

Keywords

Negative Selection Thymic Epithelial Cell Bone Marrow Chimera Thymic Epithelium Treg Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by institutional grants from the Inserm and by the EuroThymaide consortium (contract # LSHB-CT-2003-503410).

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Paola Romagnoli
  • Julie Ribot
  • Julie Tellier
  • Joost P.M. van Meerwijk
    • 1
  1. 1.Tolerance and Autoimmunity section, Centre de Physiopathologie de Toulouse PurpanInstitut National de la Santé et de la Recherche Médicale (Inserm) U563France

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