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

Thymoma is known to contain CD4(+)CD8(+) T cells, indicating that neoplasti c 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 d evelopment in thymoma and that IFN-gamma-induced HLA-DR expression on cultu red thymic epithelial cells (TEC) derived from thymoma is decreased when co mpared 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 st udy, we attempted to elucidate whether CIITA is responsible for the impaire d 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 thymom a TEC than in normal TEC. The induced levels of invariant chain (Ii) and HL A-DR in thymoma TEC were correlated with CIITA expression. The proportion o f CD3(+) cells in the CD4(+)CD8(-) subset in thymoma was also correlated wi th CIITA expression. A gel mobility shift assay however, revealed transloca tion of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellula r adhesion molecule-1 was up-regulated in the thymoma TEC to a level simila r to normal TEC in response to IFN-gamma. These results indicate that impai red up-regulation of HLA-DR in response to IFN-gamma results from insuffici ent induction of CIITA, but not from the signal from IFN-gamma receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaire d induction of CIITA may affect CD4(+) T cell development in thymoma.