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

First Author  Thyagarajan HM Year  2018
Journal  PLoS One Volume  13
Issue  7 Pages  e0200765
PubMed ID  30024927 Mgi Jnum  J:264102
Mgi Id  MGI:6192218 Doi  10.1371/journal.pone.0200765
Citation  Thyagarajan HM, et al. (2018) CCR8 is expressed by post-positive selection CD4-lineage thymocytes but is dispensable for central tolerance induction. PLoS One 13(7):e0200765
abstractText  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.
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