Quantitative analysis of immunocompetent cells in oral submucous fibrosis in Taiwan

Previous studies have shown that the local and systemic upregulation of inflammatory and fibrogenic cytokines and downregulation of antifibrotic cytokines are central to the pathogenesis of oral submucous fibrosis (OSF). The immunocompetent cells, especially the macrophages and lymphocytes, are likely the main source of cytokine synthesis. Therefore, this study used an immunohistochemical method to quantify the T lymphocyte, B lymphocyte and macrophage densities in the epithelium and subepithelial connective tissue of 50 specimens of moderately advanced and advanced OSF and 10 specimens of normal oral mucosa (NOM). The mean T lymphocyte, B lymphocyte and macrophage densities in OSF specimens were 555.2+/-417.4, 63.4+/-44.3 and 66.9+/-76.4 cells/mm(2) in the subepithelial connective tissue and 308.1+/-261.1, 1.4+/-3.5 and 6.6+/-11.9 cells/mm(2) in the epithelium, respectively. These findings suggest that T lymphocytes were the major immunocompetent cells in both the subepithelial connective tissue and epithelium of OSF specimens. Macrophages and B lymphocytes are the minor immunocompetent cells in the subepithelial connective tissue and are only occasionally found in the epithelium of OSF specimens. Similar distribution of immunocompetent cells was also found in NOM specimens. However, the mean T lymphocyte, B lymphocyte and macrophage densities in the subepithelial connective tissue (271.2+/-107.0, 13.3+/-18.4 and 17.3+/-19.1 cells/mm(2), respectively) and the mean T lymphocyte density in the epithelium (97.7+/-51.4) of NOM specimens were significantly lower than the corresponding mean cell densities in OSF specimens. Using frozen tissue sections, we further quantified the CD4+ and CD8+ lymphocyte numbers in eight moderately advanced or advanced OSF specimens. It was found that the CD4+ and CD8+ lymphocyte densities were 213.3+/-140.7 and 101.5+/-72.8 cells/mm(2) in the subepithelial connective tissue of OSF specimens, respectively. The CD4+ to CD8+ lymphocyte ratio was 2.1:1. Our results showed a significant increase in the number of T lymphocytes and macrophages and a predominance of CD4+ lymphocytes over CD8+ lymphocytes in the subepithelial connective tissue of OSF specimens. We conclude that the cellular immune response may play an important role in the pathogenesis of OSF.