Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN-gamma-inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4(+) T-Cell activation

Malignant gliomas (MGs), lethal human central nervous system (CNS) neoplasm s, contain tumor infiltrating lymphocytes (TIL). Although MHC class II mole cules are frequently detected on MG cells, suggesting that they may be capa ble of antigen (Ag) presentation to CD4(+) T cells, deficiencies in CD4(+) T-cell activation are associated with these nonimmunogenic tumors. We evalu ated regulation of the MHC class II transactivator (CIITA), the key interme diate that controls class II expression, in MG cells and tested whether MG cells could process native Ag. After interferon-gamma (IFN-gamma) stimulati on, MG cells upregulated CIITA and class II molecules. IFN-gamma -inducible CIITA expression in MG cells, as well as primary human astrocytes, was dir ected by two CIITA promoters, pIV, the promoter for IFN-gamma -inducible CI ITA expression in nonprofessional antigen-presenting cells (APC), and pIII, the promoter that directs constitutive CIITA expression in B cells. Both p III and pIV directed CIITA transcription in vivo in MGs and ex vivo in IFN- gamma -activated primary MG cultures. We also demonstrate for the first tim e that MG cells can process native Ag for presentation to CD4(+) MHC class II-restricted Th1 cells, indicating that MG cells can serve as nonprofessio nal A-PC. CIITA may be a key target to modulate MHC class II expression, wh ich could augment immunogenicity, Ag presentation, and CD4(+) T-cell activa tion in MG therapy. (C) 2001 Wiley-Liss, Inc.