Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-gamma).

Abstract

Thymoma is known to contain CD4+CD8+ T cells, indicating that neoplastic epithelial cells of thymoma have a function as thymic cortical epithelium. However, it has been shown that there is an impairment of CD4+ T cell development in thymoma and that IFN-gamma-induced HLA-DR expression on cultured thymic epithelial cells (TEC) derived from thymoma is decreased when compared with the normal thymus. MHC class II transactivator (CIITA) is known to play a critical role in IFN-gamma-induced MHC II expression. In this study, we attempted to elucidate whether CIITA is responsible for the impaired up-regulation of MHC II molecules in response to IFN-gamma in thymoma TEC. A quantitative reverse transriptase-polymerase chain reaction examination revealed that the induced level of CIITA was significantly lower in thymoma TEC than in normal TEC. The induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated with CIITA expression. The proportion of CD3+ cells in the CD4+CD8- subset in thymoma was also correlated with CIITA expression. A gel mobility shift assay however, revealed translocation of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC to a level similar to normal TEC in response to IFN-gamma. These results indicate that impaired up-regulation of HLA-DR in response to IFN-gamma results from insufficient induction of CIITA, but not from the signal from IFN-gamma receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired induction of CIITA may affect CD4+ T cell development in thymoma.

• Authors: Y Kadota, M Okumura, S Miyoshi, S Kitagawa-Sakakida, M Inoue, H Shiono, Y Maeda, T Kinoshita, R Shirakura, H Matsuda
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 121 Issue 1 Pg. 59-68 (Jul 2000) ISSN: 0009-9104 [Print] England
• PMID: 10886240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DR Antigens
• MHC class II transactivator protein
• Nuclear Proteins
• RNA, Messenger
• Trans-Activators
• Intercellular Adhesion Molecule-1
• Interferon-gamma

Topics

• Adolescent
• Adult
• Aged
• Epithelial Cells (drug effects, metabolism)
• Gene Expression (drug effects)
• HLA-DR Antigens (biosynthesis, genetics)
• Humans
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Interferon-gamma (immunology, pharmacology)
• Middle Aged
• Nuclear Proteins
• Polymerase Chain Reaction (methods)
• RNA, Messenger (analysis)
• T-Lymphocytes (cytology, drug effects, immunology)
• Thymoma (blood, immunology)
• Thymus Gland (cytology)
• Thymus Neoplasms (blood, immunology)
• Trans-Activators (genetics)
• Tumor Cells, Cultured