Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies

PLoS One. 2014 Oct 21;9(10):e109995. doi: 10.1371/journal.pone.0109995. eCollection 2014.

Abstract

Aim: Thymic epithelial cells (TECs) are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies) and compare it with a map from mouse counterparts and that of rat thymic dendritic cells.

Results: Rat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/-keratin 5 (K5)+K8+CD205+ class II MHC (MHCII)+ cortical TECs (cTECs), ED18+ED21-K5-K8+Ulex europaeus lectin 1 (UEA-1)+CD205- medullary TECs (mTEC1s), and ED18+ED21+K5+K8dullUEA-1-CD205- medullary TECs (mTEC2s). Thymic nurse cells were defined in cytosmears as an ED18+ED19+/-K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE). Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area.

Conclusion: Both rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Cells, Cultured
  • Claudin-3 / immunology
  • Claudin-3 / metabolism
  • Claudin-4 / immunology
  • Claudin-4 / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Keratin-5 / immunology
  • Keratin-5 / metabolism
  • Keratin-8 / immunology
  • Keratin-8 / metabolism
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • Phenotype
  • Plant Lectins / immunology
  • Plant Lectins / metabolism
  • Rats
  • Rats, Inbred Lew
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Thymus Gland / cytology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Claudin-3
  • Claudin-4
  • DEC-205 receptor
  • Histocompatibility Antigens Class II
  • Keratin-5
  • Keratin-8
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Plant Lectins
  • Receptors, Cell Surface
  • Ulex europaeus lectins

Grants and funding

This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number 26860138 (http://www.jsps.go.jp/english/index.html) and by an official donation from Mr. Jin Sasanuma (no conflict of interest). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.