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

PloS One
Hiran M ThyagarajanLauren I Richie Ehrlich

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...Continue Reading

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Citations

Feb 17, 2021·Journal for Immunotherapy of Cancer·Helena Van DammeJo Agnes Van Ginderachter
Mar 25, 2021·Cancer Research·Joseph R CampbellRuth Y Lan

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Methods Mentioned

BETA
FACS
flow cytometry
Fluorescence
transgenic
fluorescence microscopy

Software Mentioned

Prism
MATLAB
LasX
Imaris
GraphPad
PraireView
FlowJo

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