Experiments were performed to determine the role of the immune response in rat periodontal disease. Germ-free rats were fed defined antigen-free liquid diets or a diet containing ovalbumin(OVA) as a prototype antigen. The OVA-fed rats demonstrated increased gingival lymphocytes (mainly T at early times), OVA-sensitized spleen cells, and increased periodontal bone loss. In further studies, rats pre-sensitized with OVA, and receiving OVA in the diet, showed elevated IgG antibody, sensitized spleen cells, and elevated periodontal bone loss scores. The concept that bone loss was due to mixed hypersensitivity reaction is consistent with the periodontal pathology. The effects of pre-immunization with A. actinomycetemcomitans (Aa) on periodontal bone loss in Actinobacillus (Aa) - infected rats was examined. Delayed hypersensitivity (DTH) was present in immunized rats throughout the experimental period. Sham-immunized rats showed DTH after 30 days of infection. In addition, immunized rats showed elevated bone loss scores. These experiments support the contention that a combination of hypersensitivity reactions (i.e., mixed hypersensitivity to Aa) could give rise to the periodontal pathology observed.
Congenitally athymic rats (nude) were shown to have more periodontal bone loss than did normal littermates. However, bone loss in thymus-cell reconstituted nude rats was not different from that in control rats. Normal rats receiving Aa-sensitized T lymphocytes prior to infection with Aa demonstrated increased DTH and periodontal bone loss. These studies support the concept that T-cell functions and thymic regulation of immune responses can exert protective and/or destructive effects in periodontal disease. In order to modify disease, it will be necessary to enhance the protective aspects of the immune response and to minimize the detrimental aspects.
Get full access to this article
View all access options for this article.
References
1.
Horton, J.E. ; Oppenheim, J.J.; and Mergenhagen , S.E.: A Role for Cell-mediated Immunity in the Pathogenesis of Periodontal Disease, J Periodontol45:351-360, 1974.
2.
Horton, J.E. ; Raisz, L.G.; Simmons , H.A.; Oppenheim, J.J.; and Mergenhagen , S.E.: Bone Resorbing Activity in Supernatant Fluid from Cultured Human Peripheral Blood Leukocytes, Science177:793-795, 1972.
3.
WILDE, G.; COOPER, M.; and PAGE, R.C.: Host Tissue Response in Chronic Periodontal Disease. VI. The Role of Cell-mediated Hypersensitivity, J Periodont Res 12:179-196, 1977. 4. TAUBMAN, M.A.; BUCKELEW, J.M.; EBERSOLE, J.L.; and SMITH, D.J.: Periodontal Bone Loss and Immune Response to Ovalbumin in Germfree Rats Fed Antigen-Free Diet with Ovalbumin, Infect Immun 32:145-152, 1981.
4.
Ivanyi, L. and Lehner, T.: Stimulation of Lymphocyte Transformation by Bacterial Antigens in Patients with Periodontal Disease, Arch Oral Biol15:1089-1096, 1970.
5.
Patters, M.R. ; Genco, R.J.; Reed , M.J.; and Mashimo, P.A.: Blastogenic Response of Human Lymphocytes to Oral Bacterial Antigens: Comparison of Individuals with Periodontal Disease to Normal and Edentulous Patients, Infect Immun14:1213-1220,1976.
6.
Patters, M.R. ; Sedransk, N.; and Genco, R.J.: The Lymphoproliferative Response During Human Experimental Gingivitis, J Periodont Res14:269-278, 1979.
7.
Ivanyi, L.M. ; Wilton, J.M.A.; and Lehner , T.: Cell-mediated Immunity in Periodontal Disease; Cytotoxicity, Migration Inhibition and Lymphocyte Transformation Studies, Immunology22:141-145, 1972.
8.
Horton, J.E. ; Oppenheim, J.J.; and Mergenhagen , S.E.: Elaboration of Lymphotoxin by Cultured Human Peripheral Blood Leukocytes Stimulated with Dental-Plaque Deposits, Clin Exp Immunol13:383-393, 1973.
9.
Wahl, L.M.; Wahl, S.M.; Mergenhagen, S.E.; and
10.
Martin, G.R.: Collagenase Production by Lymphokine-activated Macrophages, Science187:261-263, 1975.
11.
Katz, D.H. and Benacerraf, B.: The Regulatory Influence of Activated T Cells on B Cell Responses to Antigen , Adv Immunol15:1-94, 1972.
12.
Gershon, R.K. : T Cell Control of Antibody Production, Contemp Top Immunobiol3:1-40, 1974.
13.
Cantor, H. and Weissman, I.: Development and Function of Subpopulations of Thymocytes and T Lymphocytes , Prog Allergy20:1-64, 1976.
14.
Katz, D.H.; Hamaoka, T.; and BENACERRAF, B.; Cell Interactions Between Histoincompatible T and B Lymphocytes. II. Failure of Physiologic Cooperative Interactions Between T and B Lymphocytes from Allogenic Donor Strains in Humoral Response to Hapten-Protein Conjugates , J Exp Med1:1405-1508, 1973 .
15.
Kindred, B. and Shreffler, D.C.: H-2 Dependence of Co-operation Between T and B Cells in vivo, J Immunol109: 940-943, 1972.
16.
Germain, R.N. and Benacerraf, B.: Helper and Suppressor T Cell Factors , Springer Semin Immunopathol3:93-127, 1980.
17.
Benacerraf, B.; Greene, M.I.; Sy , M.S.; and Dorf, M.E.: Suppressor T Cell Circuits, Ann NY Acad Sci392 :300-308, 1982.
18.
Blaese, R.M. : T and B Cell Immunodeficiency Diseases. In: Clinical Immunology, Vol. I, Parker, C.W., Ed., Philadelphia: W.B. Saunders, 1980 , pp. 314-375.
19.
Waldmann, T.A. and Broder, S.: Suppressor Cells on the Regulation of the Immune Response. In: Progress in Clinical Immunology, Vol. 3, Schwartz, R.S., Ed., New York: Grune and Stratton, 1977 , pp. 155-199.
20.
Mackler, B.F. ; Frostad, K.B.; Robertson , P.B.; and Levy, B.M.: Immunoglobulin Bearing Lymphocytes and Plasma Cells in Human Periodontal Disease, J Periodont Res12:37-45,1977.
21.
Seymour, G.J. and Greenspan, J.S.: The Phenotypic Characterization of Lymphocyte Subpopulations in Established Human Periodontal Disease, J Periodont Res14:39-46, 1979.
22.
Taubman, M.A. ; Buckelew, J.M.; Ebersole , J.L.; and Smith, D.J.: Periodontal Bone Loss in Ovalbumin Sensitized Germfree Rats Fed Antigen-Free Diet With Ovalbumin, J Periodont Res18:324-332, 1983.
23.
Lehner, T.: Cellular Aspects of Host Responses. Cellular Immunity in Periodontal Disease: An Overview. In: Host-Parasite Interactions in Periodontal Diseases, Genco, R.J. and Mergenhagen, S.E., Eds., Washington, D.C. : Amer. Soc. for Microbiol., 1982 , pp. 202-216.
24.
Socransky, S.S.: Microbiology of Periodontal Disease- Present Status and Future Considerations, J Periodontol48: 497-504,1977.
25.
FRANK, R.: Bacterial Penetration in the Apical Pocket Wall of Advanced Periodontitis, J Periodont Res 15:563-573, 1980. 26. SAGLIE, F.; CARRANZA, F.; NEWMAN, M.; CHING, L.; and LEWIN, K.: Identification of Tissue Invading Bacteria in Human Periodontal Disease, J Periodont Res 17:452-455, 1982. 27. ALLENSPACH-PETRZILKA, G.E. and GUGGENHEIM, B.: Bacteroides melaninogenicus Subsp. Intermedius Invades Rat Gingival Tissue, J Dent Res 61:259, 1982.
26.
Guggenheim, B.G.; Gaegauf-Zollinger , R.; Hefti, A.; and Burckhart, J.J.: The Effect of Cyclosporin A on Periodontal Disease in Rats Monoassociated with Actinomyces viscosus NY1, J Periodont Res16:26-38, 1981.
27.
Nobreus, N. ; Attstrom, R.; and Egelberg, J.: Effect of Anti-thymocyte Serum on Development of Gingivitis in Dogs, J Periodont Res9:227-235, 1974.
28.
Fitzgerald, J.E.; Gebhart, B.M.; and Birdsell , D.C.: Murine Model for Analysis of the Immune Response to Oral Colonization, J Periodont Res16:564-573, 1981.
29.
Rocklin, R.E. ; Bendtzen, K.; and Greineder, D.: Mediators of Immunity: Lymphokines and Monokines , Adv Immunol29:55-136, 1980.
30.
Nobreus, N. ; Attstrom, R.; and Egelberg, J.: Effect
31.
of Anti-thymocyte Serum on Chronic Gingival Inflammation in Dogs, J Periodont Res9:236-244, 1974.
32.
Barefoot, D.H. and Silverman, M.S.: Alveolar Bone Loss in Thymectomized Golden Hamsters, J Periodont Res48: 699-704, 1977.
33.
Rylander, H. ; Linde, J.; and Ahlestedt, S.: Experimental Gingivitis in Immunized Dogs , J Periodont Res11: 339-348, 1976.
34.
AMSTAD-JOSSI, M. and SCHROEDER, H.E.: Age Related Alterations of Periodontal Structures Around the Cementoenamel Junction and of the Gingival Connective Tissue Composition in Germ-free Rats, J Periodont Res 13 :76-90, 1978. 36. LISTGARTEN, M.A.: Similarity of Epithelial Relationships in the Gingiva of Rat and Man, J Periodontol 46:677-680, 1975. 37. IRVING, J.T.; SOCRANSKY, S.S.; and HEELEY, D.J.: Histologic Changes in Experimental Periodontal Disease in Gnotobiotic Rats and Conventional Hamsters, J Periodont Res 9: 73-80, 1974.
35.
Irving, J.T. ; Newman, M.G.; Socransky , S.S.; and Heeley, J.D.: Histologic Changes in Experimental Periodontal Disease in Rats Monoinfected with a Gram Negative Organism, Arch Oral Biol20:217-220, 1975.
36.
Listgarten, M.A.; Johnson, D.; Nowotny , A.; Tanner, A.C.R.; and Socransky , S.S.: Histopathology of Periodontal Disease in Gnotobiotic Rats Monoinfected with Eikenella corrodens , J Periodont Res13:134-148, 1978.
37.
Heijl, L.; Wennstrom, J.; and Socransky, S.S.: Periodontal Disease in Gnotobiotic Rats, J Periodont Res15 :405-419, 1980.
38.
Garant, P.R. : An Electron Microscopic Study of the Periodontal Tissues of Germfree Rats and Rats Monoinfected with Actinomyces naeslundii , J Periodont Res11 (Suppl 15):9-79, 1976.
39.
Van Der Hoeven, J.S.; Mikx, F.H.; Plasschaert , A.J.; and Maltha, J.C.: Experimental Periodontal Disease in Rats Induced by Plaque Forming Microorganisms, J Periodont Res10:143-147, 1975.
40.
Yoshie, H.; Taubman, M.A.; Ebersole, J.L.; Olson, C.L.; Smith, D.J.; and Pappo, J.: Actinobacillus actinomycetemcomitans is a B Cell Mitogen in Rats, Submitted for publication, 1984.
41.
Chen, P.; Nair, B.C.; and Genco, R.J.: Lymphocyte Activation by Actinobacillus actinomycetemcomitans and its LPS , J Dent Res60:524, 1981.
42.
Smith, S.; Bick, P.H.; Miller, G.A.; Ranney, R.R.; Rice, P.L.; Lalor, J., II; and Tew, J.G.: Polyclonal B-cell Activation: Severe Periodontal Disease in Young Adults, Clin Immunol Immunopathol16:354-366, 1980.
43.
Garant, P.R. and Cho, M.I.: Histopathogenesis of Spontaneous Periodontal Disease in Conventional Rats. III. The Mononuclear Cell Infiltrate and Cytoplasmic Changes in Associated Fibroblasts, J Periodont Res15:165-176, 1980.
tion, Immunity and Hypersensitivity, H.Z. Movat , Ed., Hagerstown, MD: Harper and Row, 1979, pp. 271-318.
46.
Taubman, M.A. ; Yoshie, H.; Wetherell , J.R., Jr.; Ebersole , J.L.; and Smith, D.J.: Immune Response and Periodontal Bone Loss in Germfree Rats Immunized and Infected with Actinobacillus actinomycetemcomitans, J Periodont Res18:393-401, 1983.
47.
Festing, M.F.W. ; May, D.; Connors , T.A.; Lovell, D.; and Sparrow, S.: An Athymic Nude Mutation in the Rat, Nature274:356-366, 1978.
48.
TAUBMAN, M.A.; EBERSOLE, J.L.; SMITH, D.J.; and SPRINGS, L.V.: The Nude Rat: Potential Model for Periodontal Disease Studies, IADR Progr & Abst 60:No. 459, 1981. 51. CRAWFORD, J.M.; TAUBMAN, M.A.; and SMITH, D.J.: The Natural History of Periodontal Bone Loss in Germ Free and Gnotobiotic Rats Infected with Periodontopathic Microorganisms, J Periodont Res 13:316-325, 1978.
49.
Yoshie, H.; Taubman, M.A.; Olson, C.L.; Ebersole, J.L.; and Smith, D.J.: Periodontal Bone Loss and Immune Characteristics of Congenitally Athymic and Thymus Cell Reconstituted Athymic Rats, J Dent Res62:273, 1983.
50.
YOSHIE, H.; TAUBMAN, M.A.; OLSON, C.L.; EBERSOLE, J.L.; SMITH, D.J.; and HARA, K.: Effect of Transfer of Actinobacillus-Sensitized T Lymphocytes on Periodontal Bone in Infected Rats, AADR Progr & Abst 62 :No. 663, 1983. 54. SALLAY, K.; SANAVI, F.; RING, I.; PHAM, P.; BEHLING, U.H.; and NOWOTNY, A.: Alveolar Bone Destruction in the Immunosuppressed Rat, J Periodont Res 17:263-274, 1982. 55. MACKLER, B.F.; ALTMAN, L.C.; WAHL, S.; ROSEN-STREICH, J.J.; OPPENHEIM, J.J.; and MERGENHAGEN, S.E.: Blastogenesis and Lymphokine Synthesis by T and B Lymphocytes from Patients with Periodontal Disease, Infect Immun 10:844-850, 1974.
51.
Rocklin, E.W. ; MacDermott, R.P.; Chess , L.; Schloss-Man, S.F.; and David, J.R.: Studies on Mediator Production by Highly Purified Human T and B Lymphocytes , J Exp Med140:1303-1316, 1974 .
52.
Chen, P.; Trummel, C.; Horton, J.; Baker, J.J.; and Oppenheim, J.J.: Production of Osteoclast Activating Factor by Normal Human Peripheral Blood Rosetting and Nonrosetting Lymphocytes, Eur J Immunol6:732-736.
53.
Mangan, D.R. and Lopatin, D.E.: In vitro Stimulation of Immunoglobulin Production from Human Peripheral Blood Lymphocytes by a Soluble Preparation of Actinomyces viscosus, Infect Immun31:236-244, 1981.
54.
Clagett, J. ; Engel, D.; and Chi , E.: In vitro Expression of Immunoglobulin M and G Subclasses by Murine B Lymphocytes in Response to a Polyclonal Activator from Actinomyces, Infect Immun29:234-243, 1980.
55.
Hoffman, M.M. and Schour, I.: Quantitative Studies in the Development of the Rat Molar. II. Alveolar Bone, Cementum, and Eruption, Am J Orthod26:854-874, 1940.
