Background: T cells are fundamental in the pathogenesis of periodontal disease. Suppression of cell-mediated responses is associated with disease progression together with the concomitant increase in plaque pathogens including Porphyromonas gingivalis. The aim of the present study was to examine gene expression in T cells in response to P. gingivalis in mice.
Methods: BALB/c mice were given weekly intraperitoneal injections of P. gingivalis outer-membrane antigens with Freund's incomplete adjuvant for 3 weeks, whereas control mice received phosphate buffered saline (PBS) and adjuvant only. Splenic CD4 and CD8 subpopulations were isolated by magnetic cell separation and their responses investigated using microarray analysis.
Results: Most genes coded for enzymes concerned with metabolic pathways. Only five and 28 genes, respectively, were upregulated in CD4 and CD8 cells extracted from P. gingivalis-immunized mice, including immunoglobulin (Ig) heavy-chain genes for IgG1 and IgG2a in CD4 cells. In contrast, 1,141 and 1,175 genes, respectively, were downregulated. A total of 60 and 65 genes, respectively, coded for immune response proteins or those relevant to periodontal disease pathogenesis. The overlap of genes in the two subsets was 21%. One of the major effects, apart from T-cell function suppression, was the shift away from Th1 responses, although there was also a downregulation of two genes and upregulation of one Th2-response gene. Genes downregulated included those encoding cytokines, proteins involved in Ig binding, antigen presentation, innate immunity, extracellular matrix, and cell adhesion molecules that could result in dysregulation in the progressive periodontal lesion.
Conclusions: Early findings in humans demonstrated that periodontopathic bacteria induce immunosuppressive effects on T cells. The present study has shown that P. gingivalis had a predominant downregulatory effect on gene expression in CD4 and CD8 T cells in mice.