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TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers
To maintain immune tolerance, regulatory T cell (Treg) numbers must be closely indexed to the number of conventional T cells (Tconvs) so that an adequate Treg:Tconv ratio can be maintained. Two factors important in this process are the cytokine interleukin‐2 (IL‐2) and T cell receptor (TCR) stimulat...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879461/ https://www.ncbi.nlm.nih.gov/pubmed/27891224 http://dx.doi.org/10.1002/iid3.100 |
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author | Leichner, Theresa M. Satake, Atsushi Kambayashi, Taku |
author_facet | Leichner, Theresa M. Satake, Atsushi Kambayashi, Taku |
author_sort | Leichner, Theresa M. |
collection | PubMed |
description | To maintain immune tolerance, regulatory T cell (Treg) numbers must be closely indexed to the number of conventional T cells (Tconvs) so that an adequate Treg:Tconv ratio can be maintained. Two factors important in this process are the cytokine interleukin‐2 (IL‐2) and T cell receptor (TCR) stimulation by major histocompatibility complex class II (MHC‐II). Here, we report that in addition to TCR stimulation of Tregs themselves, the maintenance of Tregs also requires TCR signaling by Tconvs. We found that Tconvs produce IL‐2 in response to self‐peptide‐MHC‐II complexes and that Tconvs possessing more highly self‐reactive TCRs express more IL‐2 at baseline. Furthermore, selective disruption of TCR signaling in Tconvs led to a trend toward decreased expression of IL‐2 and attenuated their ability to maintain Treg numbers. These data suggest that in order to maintain an adequate Treg:Tconv ratio, Tregs are continuously indexed to self‐peptide‐MHC‐II‐induced TCR signaling of Tconvs. These results have implications in attempts to modulate immune tolerance, as Treg numbers adjust to the self‐reactivity, and ultimately IL‐2 production by the T cells around them. |
format | Online Article Text |
id | pubmed-4879461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48794612016-11-25 TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers Leichner, Theresa M. Satake, Atsushi Kambayashi, Taku Immun Inflamm Dis Original Research To maintain immune tolerance, regulatory T cell (Treg) numbers must be closely indexed to the number of conventional T cells (Tconvs) so that an adequate Treg:Tconv ratio can be maintained. Two factors important in this process are the cytokine interleukin‐2 (IL‐2) and T cell receptor (TCR) stimulation by major histocompatibility complex class II (MHC‐II). Here, we report that in addition to TCR stimulation of Tregs themselves, the maintenance of Tregs also requires TCR signaling by Tconvs. We found that Tconvs produce IL‐2 in response to self‐peptide‐MHC‐II complexes and that Tconvs possessing more highly self‐reactive TCRs express more IL‐2 at baseline. Furthermore, selective disruption of TCR signaling in Tconvs led to a trend toward decreased expression of IL‐2 and attenuated their ability to maintain Treg numbers. These data suggest that in order to maintain an adequate Treg:Tconv ratio, Tregs are continuously indexed to self‐peptide‐MHC‐II‐induced TCR signaling of Tconvs. These results have implications in attempts to modulate immune tolerance, as Treg numbers adjust to the self‐reactivity, and ultimately IL‐2 production by the T cells around them. John Wiley and Sons Inc. 2016-03-24 /pmc/articles/PMC4879461/ /pubmed/27891224 http://dx.doi.org/10.1002/iid3.100 Text en © 2016 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Leichner, Theresa M. Satake, Atsushi Kambayashi, Taku TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers |
title | TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers |
title_full | TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers |
title_fullStr | TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers |
title_full_unstemmed | TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers |
title_short | TCR signaling by conventional CD4(+) T cells is required for optimal maintenance of peripheral regulatory T cell numbers |
title_sort | tcr signaling by conventional cd4(+) t cells is required for optimal maintenance of peripheral regulatory t cell numbers |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879461/ https://www.ncbi.nlm.nih.gov/pubmed/27891224 http://dx.doi.org/10.1002/iid3.100 |
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