Background:Cell interaction between dendritic cells (DC) and natural killer (NK) cells in the periodontal milieu is not yet fully known, although these cells are individually known to contribute to the pathogenesis of periodontal disease.Materials and Methods:Fifty subjects (25 males and 25 females) were included in the study. The subjects were divided into three groups: Group A comprised 16 subjects with clinically healthy gingiva; group B 17 subjects with gingivitis; and group C 17 subjects with gingivitis; and group C 17 subjects with moderate periodontitis (PPD ≥ 5 mm and CAL ≥ 3 mm in at least six sites). Gingival samples were collected and immunohistochemical study was done using CD57 and CD1a antibody. Statistical analysis was done using analysis of variance (ANOVA), followed by Tukey-Kramer multiple comparison for CD1a and Tukey's highly significant difference (HSD) test for CD57.Results and Conclusion:The study showed an inverse relationship between the CD1a+ (langerhans) cells and CD57+ (natural killer) cells. There was a significant increase in CD57+ cells and reduction in CD1a levels as periodontal disease progressed. The significant reduction in CD1a levels in periodontal disease when compared to health could possibly be a result of NK cells down regulating it. Reduction in CD1a levels may result in a low inflammatory response subsequently resulting in tissue destruction.