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      The mechanisms shaping the repertoire of CD4 + Foxp3 + regulatory T cells

      , 1 , 2

      Immunology

      John Wiley and Sons Inc.

      regulation/suppression, T cell, T‐cell receptors

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          Summary

          Regulatory T (Treg) cells expressing Foxp3 transcription factor control homeostasis of the immune system, antigenic responses to commensal and pathogenic microbiota, and immune responses to self and tumour antigens. The Treg cells differentiate in the thymus, along with conventional CD4 + T cells, in processes of positive and negative selection. Another class of Treg cells is generated in peripheral tissues by inducing Foxp3 expression in conventional CD4 + T cells in response to antigenic stimulation. Both thymic and peripheral generation of Treg cells depends on recognition of peptide/ MHC ligands by the T‐cell receptors ( TCR) expressed on thymic Treg precursors or peripheral conventional CD4 + T cells. This review surveys reports describing how thymus Treg cell generation depends on the selecting peptide/ MHC ligands and how this process impacts the TCR repertoire expressed by Treg cells. We also describe how Treg cells depend on sustained signalling through the TCR and how they are further regulated by Foxp3 enhancer sequences. Finally, we review the impact of microbiota‐derived antigens on the maintenance and functionality of the peripheral pool of Treg cells.

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          Author and article information

          Contributors
          pkraj@odu.edu , lignatowicz@gsu.edu
          lignatowicz@gsu.edu
          Journal
          Immunology
          Immunology
          10.1111/(ISSN)1365-2567
          IMM
          Immunology
          John Wiley and Sons Inc. (Hoboken )
          0019-2805
          1365-2567
          22 November 2017
          March 2018
          : 153
          : 3 ( doiID: 10.1111/imm.2018.153.issue-3 )
          : 290-296
          Affiliations
          [ 1 ] Department of Biological Sciences Old Dominion University Norfolk VA USA
          [ 2 ] Institute for Biomedical Sciences Program in Translational Immunology Georgia State University Atlanta GA USA
          Author notes
          [* ] Correspondence: Piotr Kraj, Department of Biological Sciences, Old Dominion University, 110 Mills Godwin Building, Norfolk, VA 23529, USA. Email: pkraj@ 123456odu.edu

          Senior authors: Piotr Kraj and Leszek Ignatowicz, Email: lignatowicz@ 123456gsu.edu

          Article
          PMC5795179 PMC5795179 5795179 IMM12859
          10.1111/imm.12859
          5795179
          29106696
          © 2017 John Wiley & Sons Ltd
          Page count
          Figures: 0, Tables: 1, Pages: 7, Words: 5507
          Funding
          Funded by: NIH
          Award ID: AI121151
          Award ID: DK099264
          Categories
          Review Article
          Review Articles
          Custom metadata
          2.0
          imm12859
          March 2018
          Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2 mode:remove_FC converted:02.02.2018

          T cell, regulation/suppression, T‐cell receptors

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