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Immunity. 2014 Sep 18;41(3):414-426. doi: 10.1016/j.immuni.2014.08.007. Epub 2014 Sep 11.

Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus.

Author information

1
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
3
Howard Hughes Medical Institute and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: chsieh@wustl.edu.

Abstract

The contribution of thymic antigen-presenting-cell (APC) subsets in selecting a self-tolerant T cell population remains unclear. We show that bone marrow (BM) APCs and medullary thymic epithelial cells (mTECs) played nonoverlapping roles in shaping the T cell receptor (TCR) repertoire by deletion and regulatory T (Treg) cell selection of distinct TCRs. Aire, which induces tissue-specific antigen expression in mTECs, affected the TCR repertoire in a manner distinct from mTEC presentation. Approximately half of Aire-dependent deletion or Treg cell selection utilized a pathway dependent on antigen presentation by BM APCs. Batf3-dependent CD8α⁺ dendritic cells (DCs) were the crucial BM APCs for Treg cell selection via this pathway, showing enhanced ability to present antigens from stromal cells. These results demonstrate the division of function between thymic APCs in shaping the self-tolerant TCR repertoire and reveal an unappreciated cooperation between mTECs and CD8α⁺ DCs for presentation of Aire-induced self-antigens to developing thymocytes.

PMID:
25220213
PMCID:
PMC4175925
DOI:
10.1016/j.immuni.2014.08.007
[Indexed for MEDLINE]
Free PMC Article

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