Depressed Responsiveness of Peripheral Blood Mononuclear Cells to Heat-shock Proteins in Periodontitis Patients

Abstract

The extensive homology between human and bacterial heat shock proteins (HSPs) may play a role in autoimmune reactions in periodontitis. Thus, we questioned whether peripheral blood mononuclear cell (PBMC) proliferative responses to HSPs are different between periodontitis patients and control subjects with gingivitis. The proliferative responses of PBMCs of patients (n = 10) and controls (n = 12) to recombinant mycobacterial HSP60 (MycHSP60) and HSP70 (MycHSP70), as well as recombinant human HSP60 (HumHSP60) and HSP70 (HumHSP70), were investigated. In addition, the proliferative responses to Candida albicans and purified protein derivatives of Mycobacterium (PPD) were included. Mean responses to HumHSP60, MycHSP60, and HumHSP70 were significantly lower for patients compared with controls. The responses to MycHSP70 showed a similar trend. However, when Candida and PPD were used as antigens, there was no difference in responses of the PBMCs between the periodontitis patients and controls. The level of IFN-γ in the supernatants of the cells stimulated with HSPs was lower in the patients compared with controls. This concurs with the current hypothesis that periodontitis patients have a depressed Th1 response. Furthermore, we found that with an increasing estimated subgingival bacterial load, periodontitis patients mount a decreasing immune response to HSPs, while the controls showed a positive correlation between these two parameters. From these findings, we speculate that poor reactivity to HSPs may be a susceptibility factor for destructive periodontal disease and may need to be considered in the pathogenesis of this condition.

Keywords

periodontitis heat shock protein PBMC T-lymphocytes IFN-γ

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References

Alexander MB , Damoulis PD (1994). The role of cytokines in the pathogenesis of periodontal disease. Curr Opin Periodontol 1994:39-53.

Amano A. , Sharma A. , Sojar HT , Kuramitsu HK , Genco RJ (1994). Effects of temperature stress on expression of fimbriae and superoxide dismutase by Porphyromonas gingivalis. Infect Immun 62:4682-4685.

Anderton SM , van der Zee R. , Goodacre JA (1993). Inflammation activates self hsp60-specific T cells . Euro J Immunol 23:33-38.

Anderton SM , van der Zee R. , Prakken B. , Noordzij A. , van Eden W. (1995). Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis. J Exp Med 181:943-952.

Ando T. , Kato T. , Ishihara K. , Ogiuchi H,z Okuda K. (1995). Heat shock proteins in the human periodontal disease process. Microbiol Immunol 39:321-327.

Anusaksathien O , Dolby AE (1991). Autoimmunity in periodontal diseases. J Oral Pathol Med 20:101-107.

Brandtzaeg P. , Kraus FW (1965). Autoimmunity and periodontal disease. Odontol Tidskr 73:285-293.

Chretien I. , van Kimmenade A. , Pearce MK , Banchereau J. , Abrams JS (1989). Development of polyclonal and monoclonal antibodies for immunological assays and neutralization of human IL-4. J Immunol Meth 117:67-71.

Cohen IR (1996). Heat shock protein 60 and the regulation of autoimmunity . In: Stress proteins in medicine. Van Eden W , Young DB , editors. New York: Marcel Dekker Inc., pp. 93-102.

10.

De Graeff-Meeder ER , van Eden W. , Rijkers GT , Prakken BJ , Kuis W. , Voorhorst-Ogink MM , et al. (1995). Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis. J Clin Invest 95:934-940.

11.

Ellis RJ (1996). Stress proteins as molecular chaperones. In: Stress proteins in medicine. Van Eden W , Young DB , editors. New York: Marcel Dekker Inc., pp. 1-26.

12.

Fedi PF Jr , Killoy WJ (1992). Temperature differences at periodontal sites in health and disease. J Periodontol 63:24-27.

13.

Gemmell E. , Seymour GJ (1994). Modulation of immune responses to periodontal bacteria. Curr Opin Periodontol 1994:28-38.

14.

Hirsch HZ , Tarkowski A. , Miller EJ , Gay S. , Koopman WJ , Mestecky J. (1988). Autoimmunity to collagen in adult perio

15.

dontal disease. J Oral Pathol 17:456-459.

16.

Kaufmann SH (1990). Heat shock proteins and the immune response. Immunol Today 11:129-136.

17.

Koga T. , Kusuzaki T. , Asakawa H. , Senpuku H. , Nishihara T. , Noguchi T. (1993). The 64-kilodalton GroEL-like protein of Actinobacillus actinomycetemcomitans. J Periodont Res 28 :475-477.

18.

Løkensgard I. , Bakken V. , Schenck K. (1994). Heat shock response in Actinobacillus actinomycetemcomitans . FEMS Immunol Med Microbiol 8:321-328.

19.

Lu B. , McBride BC (1994). Stress response of Porphyromonas gingivalis. Oral Microbiol Immunol 9:166-173.

20.

Lundqvist C. , Baranov V. , Teglund S. , Hammarsstrom S. , Hammarsstrom ML (1994). Cytokine profile and ultrastructure of intraepithelial γδ T cells in chronically inflamed human gingiva suggest a cytokine effector function. J Immunol 153:2302-2312.

21.

Mosmann TR , Cherwinski H. , Bond MW , Giedlin MA , Coffman RL (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J ImmunoI 136:2348-2357.

22.

Nakano Y. , Inai Y. , Yamashita Y. , Nagaoka S. , Kusuzaki-Nagira T. , Nishimura T. , et al. (1995). Molecular and immunological characterization of a 64-kDa protein of Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol 10:151-159.

23.

Petit Mda , van Steenbergen TJ , Timmerman MF , de Graaff J. , van der Velden U. (1994). Prevalence of periodontitis and suspected periodontal pathogens in families of adult periodontitis patients. J Clin Periodontol 21:76-85.

24.

Seymour GJ (1987). Possible mechanisms involved in the immunoregulation of chronic inflammatory periodontal disease. J Dent Res 66:2-9.

25.

Snyderman R. , McCarthy GA (1982). Analogous mechanisms of tissue destruction in rheumatoid arthritis and periodontal disease. In: Host-parasite interactions in periodontal diseases. Genco RJ , Mergenhagen SE , editors. Washington, DC: American Society for Microbiology , pp. 354-362.

26.

Socransky SS , Haffajee AD (1992). The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol 63:322-331.

27.

Stamm LV , Gherardini FC , Parrish EA , Moomaw CR (1991). Heat shock response of spirochetes. Infect Immun 59:1572-1575. Taubman MA, Wang H-Y, Lundqvist CA, Seymour GJ, Eastcott

28.

Tokoro Y. , Matsuki Y. , Yamamoto T. , Suzuki T. , Hara K. ( 1997). Relevance of local Th2-type cytokine mRNA expression in immunocompetent infiltrates in inflamed gingival tissue to periodontal diseases. Clin Exp Immunol 107:166-174.

29.

Van der Meide PH , Dubbeld M. , Schellekens H. (1985). Monoclonal antibodies to human immune interferon and their use in a sensitive solid phase ELISA. J Immunol Meth 79:293-305.

30.

Van der Weijden GA , Timmerman MF , Saxton CA , Russell JI , Huntington E. , van der Velden U. (1994). Intra-/inter-examiner reproducibility study of gingival bleeding. J Periodont Res 29:236-241.

31.

Van Eden W. (1991). Heat-shock proteins as immunogenic bacterial antigens with the potential to induce and regulate autoimmune arthritis. Imm Rev 121:5-28.

32.

Van Eden W. , Anderton SM , van der Zee R. , Prakken BJ , Broeren CP , Wauben MH (1996). (Altered) self peptides and the regulation of self reactivity in the peripheral T cell pool. Imm Rev 149:55-73.

33.

Vayssier C. , Mayrand D. , Grenier D. (1994). Detection of stress proteins in Porphyromonas gingivalis and other oral bacteria by Western immunoblotting analysis. FEMS Microbiol Lett 121:303-307.

34.

Wassenaar A. , Reinhardus C. , Thepen T. , Abraham-Inpijn L. , Kievits F. (1995). Cloning, characterization, and antigen specificity of T-lymphocyte subsets extracted from gingival tissue of chronic adult periodontitis patients. Infect Immun 63:2147-2153.

35.

Welch WJ , Minowada G. (1995). Clinical implications of the stress response. J Clin Invest 95:3-12.

36.

Wierenga EA , Snoek M. , de Groot C. , Chretien I. , Bos JD , Jansen HM , et al. (1990). Evidence for compartmentalization of functional subsets of CD4+ T lymphocytes in atopic patients. J Immunol 12:4651-4656.

37.

Yamazaki K. , Nakajima T. , Hara K. ( 1995). Immunohistological analysis of T cell functional subsets in chronic inflammatory disease. Clin Exp Immunol 99:384-391.

38.

Young RA , Elliott TJ (1989). Stress proteins, infection and immune surveillance . Cell 59:5-8.