Regulation of Th-POK and Runx3 in T cell development in human thymoma

Autoimmunity. 2009;42(8):653-60. doi: 10.3109/08916930903120941.

Abstract

Thymoma is a thymic epithelial neoplasm which induces T cell development. However, the frequency of mature CD4(+) T cells in thymomas is lower than in normal thymi. Recently, CD4/CD8 lineage commitment has been elucidated in animal model. The zinc finger transcription factor Th-POK is a critical factor to CD4(+) T cell development in CD4/CD8 lineage commitment, whereas CD8(+) T cell development requires the transcription factor Runx3. These factors antagonize in CD4/CD8 lineage commitment. In this study, we examined Th-POK and Runx3 mRNA expression in the T cell subsets of human normal thymus and thymoma. A quantitative reverse transcriptase-polymerase chain reaction examination revealed that Th-POK expression in normal thymi was higher in the CD4(+)CD8(-) subset than in the CD4(+)CD8(+) and CD4(-)CD8(+) subsets. In thymomas, Th-POK expression in the CD4(+)CD8(-) subset was significantly lower than that in normal thymi, and was significantly correlated with the proportion of CD3(+) cells in the CD4(+)CD8(-) subset. However, Th-POK expressions of the CD3(+)CD4(+)CD8(+) and CD3(+)CD4(+)CD8(-) subsets were not impaired in thymomas compared to normal thymi. These results suggest that thymoma neoplastic epithelial cells can induce Th-POK expression similarly to the normal thymic epithelial cells. In addition, there was no significant difference in Runx3 expression between normal thymi and thymomas. Therefore, CD4/CD8 lineage commitment dependent on Th-POK and Runx3 system seems to be working even in the neoplastic environment formed by human thymomas.

MeSH terms

  • Adult
  • Aged
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Count
  • Cell Differentiation / immunology
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation* / immunology
  • Humans
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Thymoma / genetics*
  • Thymoma / immunology
  • Thymoma / pathology*
  • Thymoma / surgery
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcription Factors / genetics*

Substances

  • CD3 Complex
  • Core Binding Factor Alpha 3 Subunit
  • DNA-Binding Proteins
  • Runx3 protein, human
  • Transcription Factors
  • ZBTB7B protein, human