Mouse thymic epithelial cell lines expressing "Aire" and peripheral tissue-specific antigens reproduce in vitro negative selection of T cells

Yoshitaka Yamaguchi, Atsushi Takayanagi, Jiabing Chen, Kosuke Sakai, Jun Kudo, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In the human thymus, AIRE (autoimmune regulator) gene is expressed in a very limited type of medullary thymic epithelial cells (mTECs) and no cognate cell lines are available, hence the molecular analysis of AIRE gene function has been difficult. To improve this situation, we attempted to isolate Aire-expressing cells and established three cell lines (Aire+TEC1, Aire+TEC2, Aire+DC) from the abnormally enlarged thymus, which was developed in the transgenic mice expressing SV40 T-antigen driven by the mouse Aire gene promoter. When these Aire+ cell lines were co-cultured with fresh thymocytes, they adhered to the majority of thymocytes and induced apoptosis as if negative selection of T-cells in the thymus is occurring in vitro. Further analysis revealed that these Aire+ cell lines are derived from mTECs and exhibit characteristic natures of "antigen presenting cells" including several distinct abilities: to express a variety of peripheral tissue-specific antigens, to produce immunoproteasome and immunological synapse, and to express some of TNFSFs (tumor necrosis factor super families). Thus, the newly established Aire+ cell lines will be invaluable for the further detailed analysis of AIRE gene function in the central tolerance of immunity and autoimmune disease.

Original languageEnglish
Pages (from-to)2019-2030
Number of pages12
JournalExperimental Cell Research
Volume317
Issue number14
DOIs
Publication statusPublished - 2011 Aug 15

Fingerprint

Epithelial Cells
T-Lymphocytes
Antigens
Cell Line
Regulator Genes
Thymus Gland
Thymocytes
Central Tolerance
Immunological Synapses
Polyomavirus Transforming Antigens
Antigen-Presenting Cells
Transgenic Mice
Autoimmune Diseases
Immunity
Tumor Necrosis Factor-alpha
In Vitro Techniques
Apoptosis
Genes

Keywords

  • AIRE
  • Negative selection
  • Thymocytes and apoptosis
  • Tolerance

ASJC Scopus subject areas

  • Cell Biology

Cite this

Mouse thymic epithelial cell lines expressing "Aire" and peripheral tissue-specific antigens reproduce in vitro negative selection of T cells. / Yamaguchi, Yoshitaka; Takayanagi, Atsushi; Chen, Jiabing; Sakai, Kosuke; Kudo, Jun; Shimizu, Nobuyoshi.

In: Experimental Cell Research, Vol. 317, No. 14, 15.08.2011, p. 2019-2030.

Research output: Contribution to journalArticle

Yamaguchi, Yoshitaka ; Takayanagi, Atsushi ; Chen, Jiabing ; Sakai, Kosuke ; Kudo, Jun ; Shimizu, Nobuyoshi. / Mouse thymic epithelial cell lines expressing "Aire" and peripheral tissue-specific antigens reproduce in vitro negative selection of T cells. In: Experimental Cell Research. 2011 ; Vol. 317, No. 14. pp. 2019-2030.
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