CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction

Hiran M. Thyagarajan, Jessica N. Lancaster, Sergio A. Lira, Lauren I.R. Ehrlich

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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-defi-cient mice, CCR8 was not required for thymocyte differentiation, rapid motility, or negative selection.

Original languageEnglish (US)
Article numbere0200765
JournalPloS one
Volume13
Issue number7
DOIs
StatePublished - Jul 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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