Regulation of Th-POK and Runx3 in T cell development in human thymoma.
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.
Tokunaga
Toshiteru
T
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Hayashi
Akio
A
Kadota
Yoshihisa
Y
Shiono
Hiroyuki
H
Inoue
Masayoshi
M
Sawabata
Noriyoshi
N
Okumura
Meinoshin
M
D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013945:Thymoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*
D017252:CD3 Complex; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493729:Runx3 protein, human; D014157:Transcription Factors; C484225:ZBTB7B protein, human