title: Diminished forkhead box P3/CD25 double-positive T regulatory cells are associated with the increased nuclear factor-kappaB ligand (RANKL+) T cells in bone resorption lesion of periodontal disease.
abstract: Periodontal disease involves multi-bacterial infections accompanied by inflammatory bone resorption lesions. The abundant T and B lymphocyte infiltrates are the major sources of the osteoclast differentiation factor, receptor activator for nuclear factor-kappaB ligand (RANKL) which, in turn, contributes to the development of bone resorption in periodontal disease. In the present study, we found that the concentrations of RANKL and regulatory T cell (T(reg))-associated cytokine, interleukin (IL)-10, in the periodontal tissue homogenates were correlated negatively, whereas RANKL and proinflammatory cytokine, IL-1beta, showed positive correlation. Also, according to the fluorescent-immunohistochemistry, the frequency of forkhead box P3 (FoxP3)/CD25 double-positive cells was diminished strikingly in the bone resorption lesion of periodontal disease compared to healthy gingival tissue, while CD25 or FoxP3 single positive cells were still observed in lesions where abundant RANKL+ lymphocytes were present. Very importantly, few or no expressions of FoxP3 by the RANKL+ lymphocytes were observed in the diseased periodontal tissues. Finally, IL-10 suppressed both soluble RANKL (sRANKL) and membrane RANKL (mRANKL) expression by peripheral blood mononuclear cells (PBMC) activated in vitro in a bacterial antigen-specific manner. Taken together, these results suggested that FoxP3/CD25 double-positive T(reg) cells may play a role in the down-regulation of RANKL expression by activated lymphocytes in periodontal diseased tissues. This leads to the conclusion that the phenomenon of diminished CD25+FoxP3+ T(reg) cells appears to be associated with the increased RANKL+ T cells in the bone resorption lesion of periodontal disease.
authors.affiliation: Department of Immunology, The Forsyth Institute, Boston, MA 02115, USA.
authors.forename: C W O
authors.initials: CW
authors.lastname: Ernst
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Nakanishi
authors.forename: N Y
authors.initials: NY
authors.lastname: Karimbux
authors.forename: T M B
authors.initials: TM
authors.lastname: Rezende
authors.forename: P
authors.initials: P
authors.lastname: Stashenko
authors.forename: M
authors.initials: M
authors.lastname: Seki
authors.forename: M A
authors.initials: MA
authors.lastname: Taubman
authors.forename: T
authors.initials: T
authors.lastname: Kawai
mesh_terms: D000328:Adult; D001862:Bone Resorption / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005881:Gingiva / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D053583:Interleukin-1beta / Q000032:analysis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D018613:Microscopy, Confocal; D010510:Periodontal Diseases / Q000276:immunology*; D053245:RANK Ligand / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053583:Interleukin-1beta; D053645:Interleukin-2 Receptor alpha Subunit; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D016753:Interleukin-10