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

Y. Kadota, Meinoshin Okumura, S. Miyoshi, S. Kitagawa-Sakakida, M. Inoue, H. Shiono, Y. Maeda, T. Kinoshita, R. Shirakura, H. Matsuda

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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-γ-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-γ-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-γ 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 CD+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-γ. These results indicate that impaired up- regulation of HLA-DR in response to IFN-γ results from insufficient induction of CIITA, but not from the signal from IFN-γ 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.

Original languageEnglish
Pages (from-to)59-68
Number of pages10
JournalClinical and Experimental Immunology
Volume121
Issue number1
DOIs
Publication statusPublished - Jul 17 2000

Keywords

  • Invariant chain
  • MHC class II transactivator
  • T cell development
  • Thymic epithelial tumour myasthenia gravis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kadota, Y., Okumura, M., Miyoshi, S., Kitagawa-Sakakida, S., Inoue, M., Shiono, H., Maeda, Y., Kinoshita, T., Shirakura, R., & Matsuda, H. (2000). Altered T cell development in human thymorea is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-γ). Clinical and Experimental Immunology, 121(1), 59-68. https://doi.org/10.1046/j.1365-2249.2000.01256.x