Interferon-gamma-dependent immunosuppressive effects of human gingival fibroblasts

Immunoregulatory functions of human gingival fibroblasts (HGF) were examined. As in fibroblasts isolated from other tissues, HGF were activated with interferon-gamma (IFN-gamma) to express HLA-DR molecules. Despite the fact that the IFN-gamma-treated HGF showed phenotypical resemblance to so-called antigen-presenting cells (APC), the IFN-gamma-treated HGF were ineffective stimulators of alloreactive peripheral T cells. Conversely, IFN-gamma-treated HGF dramatically inhibited the proliferative responses of allogeneic APC (allo-APC) or phytohaemagglutinin (PHA)-stimulated T cells. Immunosuppressive effects of culture supernatant (CS) of IFN-gamma-treated HGF were low and were completely abrogated by the addition of indomethacin. Moreover, the production of prostaglandin E2 (PGE2) by HGF was not affected by IFN-gamma. These results suggest that IFN-gamma-dependent immunosuppressive effects of HGF were not due to PGE2 produced by HGF. In order to investigate further the mechanism(s) of IFN-gamma-dependent immunosuppressive effects of HGF, activated T cells and IFN-gamma-treated HGF were separately cultured in the same well by collagen films which were assembled in cylindrical cells and disturbed physical interactions between T cells and HGF. The proliferative responses of T cells which directly contacted with IFN-gamma-treated HGF were inhibited more significantly than those of T cells which did not contact with IFN-gamma-treated HGF. This suggests that IFN-gamma-dependent immunosuppressive effects of HGF were mediated by direct interactions between T cells and activated HGF. The present results suggest that IFN-gamma-stimulated HGF would modulate the immune responses of locally infiltrated T cells in periodontal lesions.