The present study was carried out to examine the antigen-presenting cell (APC) functions of human gingival fibroblasts (HGF) elicited with IFN gamma. Stimulation of HGF with IFN gamma clearly induced HLA-DR expression and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on HGF. Despite the phenotypical resemblance of IFN gamma-treated HGF to so-called APC, HLA-DR positive HGF were unable to induce proliferation of allo-reactive peripheral blood T cells (PBT) isolated from different donors. The failure of IFN gamma-treated HGF to stimulate unprimed allo-reactive PBT was not due to the lack of production of IL-1 or the immunosuppressive effect of PGE2 from HGF. On the other hand, the fact that detectable expression of CD80, ligand for CD28, was not found on IFN gamma-treated HGF may at least in part explain the ineffective function of HGF as APC. Interestingly, IFN gamma-treated HGF induced proliferation of primed allo-reactive CD4+ T cells in a HLA-DR dependent manner, suggesting that IFN gamma-treated HGF may have the ability to stimulate pre-activated T cells. We then confirmed that high levels of IFN gamma mRNA were detectable in inflamed gingival tissue. Although it cannot be concluded from this study that HGF are incapable of effectively presenting antigenic peptides to autologous T cells bearing appropriate T cell receptors, present results suggest that HGF may be affected by locally-secreted IFN gamma and that the IFN gamma-stimulated HGF may play a role in regulating immune responsiveness in inflammatory periodontal lesions.