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CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction
Following positive selection, thymocytes migrate into the medulla where they encounter diverse self-antigens that induce central tolerance. Thymocytes expressing T cell receptors (TCRs) with high affinity for self-antigens displayed by medullary antigen presenting cells (APCs) undergo either negativ...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053179/ https://www.ncbi.nlm.nih.gov/pubmed/30024927 http://dx.doi.org/10.1371/journal.pone.0200765 |
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author | Thyagarajan, Hiran M. Lancaster, Jessica N. Lira, Sergio A. Ehrlich, Lauren I. R. |
author_facet | Thyagarajan, Hiran M. Lancaster, Jessica N. Lira, Sergio A. Ehrlich, Lauren I. R. |
author_sort | Thyagarajan, Hiran M. |
collection | PubMed |
description | Following positive selection, thymocytes migrate into the medulla where they encounter diverse self-antigens that induce central tolerance. Thymocytes expressing T cell receptors (TCRs) with high affinity for self-antigens displayed by medullary antigen presenting cells (APCs) undergo either negative selection or diversion to the regulatory T cell (Treg) lineage, thus ensuring maturation of non-autoreactive T cells. Because many self-antigens are expressed by only a small percentage of medullary thymic epithelial cells, thymocytes must enter the medulla and efficiently scan APCs therein to encounter the full array of self-antigens that induce central tolerance. Chemokine receptors play a critical role in promoting medullary entry and rapid motility of post-positive selection thymocytes. We found that the chemokine receptor CCR8 is expressed by post-positive selection CD4(+) single positive (SP) thymocytes in mice, while the corresponding chemokine ligands are expressed by medullary APCs, and thus hypothesized that CCR8 would promote thymocyte medullary entry and/or rapid motility to induce negative selection. However, despite a subtle decline in thymocyte medullary accumulation and the presence of autoantibodies in aged CCR8-deficient mice, CCR8 was not required for thymocyte differentiation, rapid motility, or negative selection. |
format | Online Article Text |
id | pubmed-6053179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60531792018-07-27 CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction Thyagarajan, Hiran M. Lancaster, Jessica N. Lira, Sergio A. Ehrlich, Lauren I. R. PLoS One Research Article Following positive selection, thymocytes migrate into the medulla where they encounter diverse self-antigens that induce central tolerance. Thymocytes expressing T cell receptors (TCRs) with high affinity for self-antigens displayed by medullary antigen presenting cells (APCs) undergo either negative selection or diversion to the regulatory T cell (Treg) lineage, thus ensuring maturation of non-autoreactive T cells. Because many self-antigens are expressed by only a small percentage of medullary thymic epithelial cells, thymocytes must enter the medulla and efficiently scan APCs therein to encounter the full array of self-antigens that induce central tolerance. Chemokine receptors play a critical role in promoting medullary entry and rapid motility of post-positive selection thymocytes. We found that the chemokine receptor CCR8 is expressed by post-positive selection CD4(+) single positive (SP) thymocytes in mice, while the corresponding chemokine ligands are expressed by medullary APCs, and thus hypothesized that CCR8 would promote thymocyte medullary entry and/or rapid motility to induce negative selection. However, despite a subtle decline in thymocyte medullary accumulation and the presence of autoantibodies in aged CCR8-deficient mice, CCR8 was not required for thymocyte differentiation, rapid motility, or negative selection. Public Library of Science 2018-07-19 /pmc/articles/PMC6053179/ /pubmed/30024927 http://dx.doi.org/10.1371/journal.pone.0200765 Text en © 2018 Thyagarajan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Thyagarajan, Hiran M. Lancaster, Jessica N. Lira, Sergio A. Ehrlich, Lauren I. R. CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction |
title | CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction |
title_full | CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction |
title_fullStr | CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction |
title_full_unstemmed | CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction |
title_short | CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction |
title_sort | ccr8 is expressed by post-positive selection cd4-lineage thymocytes but is dispensable for central tolerance induction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053179/ https://www.ncbi.nlm.nih.gov/pubmed/30024927 http://dx.doi.org/10.1371/journal.pone.0200765 |
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