Characterization of Gingival Th1, Th2 and Th17 Cells in Murine Periodontitis Model

Abstract

Cellular and molecular mechanisms of the immune system influencing oral bone metabolism remain to be elucidated. In this study, we characterize the mucosal cytokine production by CD4+ T cells in the inflamed gingiva of mice infected with Porphyromonas gingivalis (P. gingivalis). A murine periodontal disease model with alveolar bone loss showed significant levels of FimA-specific salivary secretory IgA and plasma IgG Ab responses. Further, IL-6 and TNF-α production was elevated when compared with sham-infected mice. The frequencies of Th1 (IFN-γ), Th2 (IL-4) and Th17 (IL-17) producing CD4+ T cells were also increased in P. gingivalis infected mice. Among these cytokines, a significantly higher frequency of IFN-γ producing CD4+ T cells was noted. The kinetics of intracellular cytokine analyses revealed a significantly increased frequency of IFN-γ-, IL-4- and IL-17-producing CD4+ T cells one day after infection. Further, the frequency of IFN-γ producing CD4+ T cells was maintained throughout the experimental period. Although IL-4 and IL-17 production was intact until 15 days after the infection, the numbers of CD4+ T cells producing these cytokines were reduced thereafter. These results indicate that Th1-type CD4+ T cells play distinct roles in the induction and regulation of periodontal disease when compared with Th2- and Th17-type cytokine-producing CD4+ T cells.