INDUCTION OF CIITA AND MODIFICATION OF IN-VIVO HLA-DR PROMOTER OCCUPANCY IN NORMAL THYMIC EPITHELIAL-CELLS TREATED WITH IFN-GAMMA - SIMILARITIES AND DISTINCTIONS WITH RESPECT TO HLA-DR-CONSTITUTIVE B-CELLS

In this study, the IFN-gamma induction of MHC class II gene expression in primary cultures of thymic epithelial cells (TEC) was analyzed. Th is cellular system offers the advantage that MHC class II induction is studied in a ''physiologic'' cell lineage that, as a result of this e xpression within the thymus, is thought to participate to the selectio n and maturation of the T cells, It was found that the MHC class II ge ne expression was associated with the de novo transcription of the gen e encoding the CIITA trans-activator, a crucial MHC class II gene regu latory factor, Furthermore, the anatomy of interaction between the MHC class II DRA promoter and corresponding binding factors was analyzed by in vivo DNAse I footprint, It was found that treatment with IFN-gam ma induces changes in the occupancy of the DRA gene regulatory sequenc es by nuclear factors, The resulting occupancy displays strong similar ities with the one observed in the MHC class II-constitutive B cells, represented by both the Burkitt lymphoma line Rail and normal tonsil-d erived B cells, However, some peculiar differences were observed betwe en the TEC, either IFN-gamma-induced or not, and the constitutive B ce lls, These results suggest that both common mechanisms, such as the on e mediated by the CIITA trans-activator, and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and IFN-gamma-induced MHC class II gene expression.