Abstract
Chronic periodontitis is characterized by dense infiltrations of T lymphocytes in the connective tissue, which consists mainly of gingival fibroblasts. It is becoming increasingly clear that T lymphocytes and gingival fibroblasts are capable of influencing each other. For example, the T cell cytokine interferon-gamma (IFN-γ) is able to induce MHC class II molecules on the surface of several cell types, including gingival fibroblasts. Histological sections of chronically inflamed gingival tissue showed a great number of CD4+ and CD8+ T cells that produced IFN-γ, and in addition showed abundant expression of MHC class II molecules on gingival fibroblasts. Therefore, we investigated whether these gingival fibroblasts acquire the capacity to carry out MHC class II-restricted functions such as antigen presentation to local T cells. In this study, we show that IFN-γ-treated gingival fibroblasts were able to function as antigen-presenting cells (APC) for superantigen-mediated T cell proliferation. However, these fibroblasts failed to present whole-cell antigens of periodontitis-associated bacteria. Moreover, gingival fibroblasts inhibited the presentation of the whole-cell antigens of these bacteria by professional APC. This inhibition could be overcome by the addition of IL-2. These results suggest that gingival fibroblasts play an important role in the local specific immune response in chronic inflammatory periodontal lesions by regulating the response of infiltrating T cells.
Keywords: T lymphocytes, gingival fibroblasts, antigen presentation, periodontitis
Full Text
The Full Text of this article is available as a PDF (744.4 KB).
References
- 1.Listgarten MA. Pathogenesis of periodontitis. J Clin Periodontal. 1989;13:418–30. doi: 10.1111/j.1600-051x.1986.tb01485.x. [DOI] [PubMed] [Google Scholar]
- 2.Seymour GJ, Gemmell E, Reinhardt RA, Eastcott J, Taubman MA. Immunopathogenesis of chronic inflammatory disease: cellular and molecular mechanisms. J Periodont Res. 1993;28:478–86. doi: 10.1111/j.1600-0765.1993.tb02108.x. [DOI] [PubMed] [Google Scholar]
- 3.Zadeh HH, Kreutzer DL. Evidence for involvement of superantigens in human periodontal diseases: skewed expression of T cell receptor variable regions by gingival T cells. Oral Microbiol Immunol. 1996;11:88–95. doi: 10.1111/j.1399-302x.1996.tb00341.x. [DOI] [PubMed] [Google Scholar]
- 4.Getka TP, Alexander DCC, Parker WB, Miller GA. Immunomodulatory and superantigen activities of bacteria associated with adult periodontitis. J Periodontal. 1996;67:909–17. doi: 10.1902/jop.1996.67.9.909. [DOI] [PubMed] [Google Scholar]
- 5.Genco RJ. Host responses in periodontal diseases: current concepts. J Periodontal. 1992;63:338–55. doi: 10.1902/jop.1992.63.4s.338. [DOI] [PubMed] [Google Scholar]
- 6.Hayashi J, Saito I, Ishikawa I, Miyasaka N. Effects of cytokines and periodontopathic bacteria on the leukocyte function-associated antigen 1/intercellular adhesion molecule 1 pathway in gingival fibroblasts in adult periodontitis. Infect Immun. 1994;62:5205–12. doi: 10.1128/iai.62.12.5205-5212.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Takahashi K, Takigawa M, Takashiba S, Nagai A, Miyamoto M, Kurihara H, Murayama Y. Role of cytokine in die induction of adhesion molecules on cultured human gingival fibroblasts. J Periodontal. 1994;65:230–5. doi: 10.1902/jop.1994.65.3.230. [DOI] [PubMed] [Google Scholar]
- 8.Wassenaar A, Reinhardus C, Thepen T, Abraham-Inpijn L, Kievits F. Cloning, characterization, and antigen specificity of T-lymphocyte subsets extracted from gingival tissue of chronic adult periodontitis patients. Infect Immun. 1995;63:2147–53. doi: 10.1128/iai.63.6.2147-2153.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Lundqvist C, Baranov V, Teglund S, Hammarstrom S, Hammarstrom M. Cytokine profile and ultrastructure of intraepithelial γ δ T cells in chronically inflamed gingiva suggest a cytotoxic effector function. J Immunol. 1994;153:2302–12. [PubMed] [Google Scholar]
- 10.Crawford JM. Distribution of ICAM-1, LFA-3 and HLA-DR in healthy and diseased gingival tissues. J Periodont Res. 1992;27:291–8. doi: 10.1111/j.1600-0765.1992.tb01680.x. [DOI] [PubMed] [Google Scholar]
- 11.Kraft M, Filsinger S, Krämer KL, Kabelitz D, Hänsch GM, Schoels M. Synovial fibroblasts as accessory cells for staphylococcal enterotoxin-mediated T-cell activation. Immunology. 1995;85:461–6. [PMC free article] [PubMed] [Google Scholar]
- 12.Origuchi T, Eguchi K, Kawabe Y, Mizokami A, Ida H, Nagataki S. Synovial cells are potent antigen-presenting cells for superantigen, staphylococcal enterotoxin B (SEB) Clin Exp Immunol. 1995;99:345–51. doi: 10.1111/j.1365-2249.1995.tb05556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Boots AMH, Wimmers-Bertens AJMM, Rijnders AWM. Antigen-presenting capacity of rheumatoid synovial fibroblasts. Immunology. 1994;82:268–74. [PMC free article] [PubMed] [Google Scholar]
- 14.Van Winkelhoff AJ, Carlee AW, De Graaff J. Bacteroides endodontalis and other black-pigmented Bacteroides in odontogenic abscesses. Infect Immun. 1985;49:494–7. doi: 10.1128/iai.49.3.494-497.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.van Neerven RJJ, van de Pol MM, Wierenga EA, Aalberse RC, Jansen HM, Kapsenberg ML. Peptide-specificity and HLA-restriction do not dictate lymphokine production by allergen-specific T lymphocyte clones. Immunology. 1994;82:351–6. [PMC free article] [PubMed] [Google Scholar]
- 16.Wierenga EA, Snoek M, De Groot CJ, Chrétien I, Bos JD, Jansen HM, Kapsenberg ML. Evidence for compartmentalization of functional subsets of CD4+ T lymphocyte clones from atopic and non-atopic patients. J Immunol. 1990;144:4651–6. [PubMed] [Google Scholar]
- 17.Gillis S, Ferm W, Ou W, Smith KA. T cell growth factor: parameters of production and quantitative microassay for activity. J Immunol. 1978;120:2027–31. [PubMed] [Google Scholar]
- 18.Geppert TD, Lipsky PE. Antigen presentation by interferon-γ-treated endothelial cells and fibroblasts: differential ability to function as antigen-presenting cells despite comparable la expression. J Immunol. 1985;135:3750–62. [PubMed] [Google Scholar]
- 19.Umetsu DT, Pober JS, Jabara HH, Fiers W, Yunis EJ, Burakoff J, Reiss CS, Geha RS. Human dermal fibroblasts present tetanus toxoid antigen to antigen-specific T cell clones. J Clin Invest. 1985;76:254–60. doi: 10.1172/JCI111955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Wassenaar A, Reinhardus C, Abraham-Inpijn L, Kievits F. Type-1 and type-2 CD8+ T-cell subsets isolated from chronic adult periodontitis tissue differ in surface phenotype and biological functions. Immunology. 1996;87:113–8. [PMC free article] [PubMed] [Google Scholar]
- 21.Flynn MJ, Slots J. Beta-hemolytic streptococci in advanced periodontitis. Oral Microbiol Immunol. 1993;8:295–7. doi: 10.1111/j.1399-302x.1993.tb00577.x. [DOI] [PubMed] [Google Scholar]
- 22.Rams TE, Feik D, Slots J. Staphylococci in human periodontal diseases. Oral Microbiol Immunol. 1990;5:29–32. doi: 10.1111/j.1399-302x.1990.tb00222.x. [DOI] [PubMed] [Google Scholar]
- 23.Grass HJ, Scott C, Rollins BJ, Brach MA, Hermann F. Human fibroblasts express functional IL-2 receptors formed by the IL-2R α- and β-chain subunits. Association of IL-2 binding with secretion of the monocyte chemoattractant protein-1. J Immunol. 1996;157:851–7. [PubMed] [Google Scholar]
- 24.Shimabukuru Y, Murakami S, Okada H. Interferon-gamma-dependent immuno-suppressive effects of human gingival fibroblasts. Immunology. 1992;76:344–7. [PMC free article] [PubMed] [Google Scholar]
- 25.Shimabukuru Y, Murakami S, Okada H. Antigen-presenting-cell function of interferon 7-treated human gingival fibroblast. J Periodontal Res. 1996;31:217–28. doi: 10.1111/j.1600-0765.1996.tb00486.x. [DOI] [PubMed] [Google Scholar]
- 26.Nickoloff BJ, Mitra RS, Green J, Zheng XG, Shimizu Y, Thompson C, Turka LA. Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. J Immunol. 1993;150:2148–59. [PubMed] [Google Scholar]
- 27.Rott O, Tontsch U, Fleischer B. Dissociation of antigen-presenting capacity of astrocytes for peptide-antigens versus superantigens. J Immunol. 1993;150:87–95. [PubMed] [Google Scholar]
- 28.Liu H, Lampe MA, Iregui MV, Cantor H. Conventional antigen and super-antigen may be coupled to distinct and cooperative T-cell activation pathways. Proc Natl Acad Sci USA. 1991;88:8705–9. doi: 10.1073/pnas.88.19.8705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.McFarlane CG, Meikle MC. Interleukin-2, interleukin-2 receptor and interleukin-4 levels are elevated in the sera of patients with periodontal disease. J Periodont Res. 1991;26:402–8. doi: 10.1111/j.1600-0765.1991.tb01729.x. [DOI] [PubMed] [Google Scholar]
- 30.Yamazaki K, Nakajima T, Hara K. Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease. Clin Exp Immunol. 1995;99:384–91. doi: 10.1111/j.1365-2249.1995.tb05562.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Saglie FR, Pertuiset J, Rezende MT, Nestor M, Marfany A, Cheng J. In situ correlative immuno-identification of mononuclear infiltrates and invasive bacteria in diseased gingiva. J Periodontal. 1988;59:688–96. doi: 10.1902/jop.1988.59.10.688. [DOI] [PubMed] [Google Scholar]
