The adaptive immune system consists of humoral and cell-mediated immunity. T-lymphocytes are the key components of cell-mediated immunity. CD4+ helper T-lymphocytes facilitate B-cells to differentiate and produce specific antibodies, whereas CD8+ cytotoxic T-lymphocytes kill virally infected cells. Periodontal diseases have been associated with a variety of imbalances in the regulation of immune responses. Changes in the ratios of peripheral blood CD4+ and CD8+ T-lymphocytes, depressed proliferative responses of peripheral blood lymphocytes, and increased frequency of CD45RO+ memory T-lymphocytes in diseased tissues have been reported in individuals with various forms of periodontal disease. While some studies have shown an increased frequency of γδ+ T-cells in periodontal lesions, the role of γδ+ T-cells in periodontal disease remains controversial. The ability of putative periodontopathic bacteria selectively to stimulate certain V(3-expressing T-cells is intriguing and could determine whether a CD4+ Th I or a CD4+ Th2 cell response is elicited. The prominence of a particular subset of helper T-cells within the periodontal lesion could be a reflection of the stage and activity of the disease, or the types of bacteria present. Regardless, longitudinal studies of the involvement of T-cell subsets and cytokines in periodontal disease are clearly needed.
References
1.
Abe J., Kotzin BL, Jujo K., Melish ME, Glode MP, Kohsaka T., et al. (1992). Selective expansion of T-cells expressing T-cell receptor variable regions Vβ2 and Vβ8 in Kawasaki disease. Proc Natl Acad Sci (USA)89:4066-4070.
2.
Afar B., Engel D., Clark EA (1992). Activated lymphocyte subsets in adult periodontitis. J Periodont Res27:126-133.
3.
Amer A., Singh G., Darke C., Colby AE (1990). Spontaneous lymphocyte proliferation in severe periodontal disease: role of T and B cells. J Oral Pathol Med19:49-52.
4.
Babbitt B., Allen P., Matsueda G., Haber E., Unanue E. (1985). Binding of immunogeneic peptides to la histocompatibility molecules. Nature317:359-361.
5.
Baker JJ, Tondreau SP (1985). The stimulation of human peripheral blood lymphocytes by oral bacteria: macrophage and T-cell dependence. J Dent Res64:906-912.
6.
Barnes PF, Abrams JS, Lu S., Sieling PA, Rea TH, Modlin RL (1993). Patterns of cytokine production by Mycobacterium-reactive human T-cell clones. Infect Immun61:197-203.
7.
Bloom BR, Modlin R.), Salgame P. (1992). Stigma variations: observations on suppressor T cells and leprosy. Ann Rev Immunol10:453-488.
8.
Boyatzis S., Seymour G.) (1986). Effect of age and periodontal status in man on the spontaneous proliferation of peripheral blood lymphocytes. Arch Oral Biol31:749-755.
9.
Buus S., Sette A., Colon S., Miles C., Grey H. ( 1987). The relationship between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science235:1353-1358.
10.
Celenligil H., Kansu E., Eratalay K., Yavuzyilmaz E. (1987). Prepubertal periodontitis. A case report with an analysis of lymphocyte populations. J Clin Periodontol14:85-88.
11.
Celenligil H., Kansu E., Eratalay K. (1990a). Juvenile and rapidly progressive periodontitis. Peripheral blood lymphocyte subpopulations. J Clin Periodontol17:207-210.
12.
Celenligil H., Kansu E., Ruacan S., Eratalay K., Caglayan G. (1990b). Immunohistological analysis of gingival lymphocytes in adult periodontitis. J Clin Periodontol17:542-548.
13.
Celenligil H., Kansu E., Ruacan S., Eratalay K., Caglayan G. (1993). In situ characterization of gingival mononuclear cells in rapidly progressive periodontitis. J Periodontol64:120-127.
14.
Choi Y., Kotzin B., Herron L., Callahan J., Marrack P., Kappler ) (1989). Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc Natl Acad Sci (USA)86:8941-8945.
15.
Cobb CM, Singla 0, Feil PH, Theisen FC, Schultz RE ( 1989). Comparison of NK-cell (Leu-7+ and Leu-11b+) populations in clinically healthy gingiva, chronic gingivitis and chronic adult periodontitis. J Periodont Res 24:1-7.
16.
Cobb CM, Singla O., Theisen FC, Shultz RE (1990). Ultrastructural evidence of large granular lymphocyte (LGL) activity in lesions of chronic adult periodontitis. J Clin Periodontol17:371-378.
17.
Cole KL, Seymour GJ Powell RN (1987). Phenotypic and functional analysis of T cells extracted from chronically inflamed human periodontal tissues. ) J Periodontol58:569-573.
18.
Davis MM, Bjorkman PJ (1988). T-cell antigen receptor genes and T-cell recognition. Nature334:395-402.
19.
Del Prete GF, De Carli M., Almerigogna F., Giudizi M-G., Biagiotti R., Romagnani S. (1993). Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol150:1-8.
20.
Engel D., Monzingo S., Rabinovitch P., Clagett J., Stone R. (1984). Mitogen-induced hyperproliferaton response of peripheral blood mononuclear cells from patients with severe generalized periodontitis: lack of correlation with proportions of T cells and T-cell subsets. Clin Immunol Immunopathol30:374-386.
21.
Evans RI, Mikulecky M., Seymour GJ (1989). Effect of initial treatment of chronic inflammatory periodontal disease in adults on spontaneous peripheral blood lymphocyte proliferation. J Clin Periodontol16:271-277.
22.
Fortune F., Walker J., Lehner T. (1990). The expression of γδ T cell receptor and the prevalence of primed, activated and IgA bound T cells in Behçet's syndrome. Clin Exp Immunol82:326-332.
23.
Fujihashi K., Beagley KW, Kono Y., Aicher WK, Yamamoto M., DiFabio S., et al. (1993). Gingival mononuclear cells from chronic inflammatory periodontal tissues produce interleukin (IL)-5 and IL-6 but not IL-2 and IL-4. Am J Pathol142:1239-1250.
24.
Fujita S., Takahashi H., Okabe H., Ozaki Y., Hara Y., Kato I. ( 1992). Distribution of natural killer cells in periodontal diseases: an immunohistochemical study. J Periodontol63:686-689.
25.
Gemmell E., Seymour GJ (1993). Interleukin 1, interleukin 6 and transforming growth factor-beta production by human gingival mononuclear cells following stimulation with Porphyromonas gingivalis and Fusobacterium nucleatum. J Periodont Res28:122-129.
26.
Gemmell E., Seymour GJ (1994). Modulation of immune responses to periodontal bacteria. Curr Opin Periodontol1994:28-38.
27.
Gemmell E., Seymour GJ (1995). Gamma-delta T lymphocytes in human periodontal disease tissue. J Periodontol66:780-785.
28.
Gemmell E., Feldner B., Seymour GJ (1992). CD45RA and CD45RO positive CD4 cells in human peripheral blood and periodontal disease tissue before and after stimulation with periodontopathic bacteria. Oral Microbiol Immunol7:84-88.
29.
Gemmell E., Sved AM, Seymour GJ (1995). Cellular adhesion molecules on periodontal lymphocytes. Austr Dent J40:129-134.
30.
Groh V., Porcelli S., Fabbi M., Lanier LL, Picker LJ, Anderson T., et al. (1989). Human lymphocytes bearing T cell receptor γ/δ are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med169:1277-1294.
31.
Haanen JB, de Waal Malefijt T., Res PC, Kraakman EM, Ottenhoff TH, de Vries RR, et al. (1991). Selection of a human T helper Type I-like subset by Mycobacteria. J Exp Med174:583-592.
32.
Haqqi TM, Anderson GD, Banerjee S., David CS (1992). Restricted heterogeneity in T-cell antigen receptor Vβ gene usage in the lymph nodes and arthritic joints of mice. Proc Natl Acad Sci (USA)89:1253-1255.
33.
Hodes RI, Novick MB, Palmer LD, Knepper JE (1993). Association of a Vβ2-specific super antigen with a tumorigenic milk-borne mammary tumor virus. J Immunol150:1422-1428.
34.
Imberti L., Sottini A., Bettinardi A., Puoti M., Primi D. (1991). Selective depletion in HIV infection of T cells that bear specific T cell receptor Vβ sequences. Science254:860-862.
35.
loannides CG, Freedman RS (1991). Selective usage of TCR Vβ in tumor-specific CTL lines isolated from ovarian tumor-associated lymphocytes. Anticancer Res11:1919-1926.
36.
Ishii T., Mahanonda R., Seymour GJ (1992). The establishment of human T cell lines reactive with specific periodontal bacteria. Oral Microbiol Immunol7:225-229.
37.
Kappler J., Kotzin B., Herron L., Gelfand EW, Bigler RD, Boylston A., et al. (1989). Vβ-specific stimulation of human T cells by staphylococcal toxins. Science244:811-813.
38.
Karp CL, El-Safi SH, Wynn TA, Satti MH, Kordofani AM, Hashim FA, et al. (1993). In vivo cytokine profiles in patients with Kala-Azar. Marked elevation of both IL-10 and IFN-gamma. J Clin Invest91:1644-1648.
39.
Katz J., Goultschin J., Benoliel R., Schlesinger M. (1988). Peripheral T lymphocyte subsets in rapidly progressive periodontitis. J Clin Periodontol15:266-268.
40.
Kawahara K., Fukunaga M., Takata T., Kawamura K., Morishita M., Iwamoto Y. (1995). Immunohistochemical study of gamma-delta T cells in human gingival tissues. J Periodontol66:775-779.
41.
Kelso A. (1995). Th1 and TH2 subsets: paradigms lost? Immunol Today16:374-379.
42.
Kimura S., Fujimoto N., Okada H. (1991). Impaired autologous mixed-lymphocyte reaction of peripheral blood lymphocytes in adult periodontitis. Infect Immun59:4418-4424.
43.
Kinane DF, Johnston RA, Evans CW (1989). Depressed helper-to-suppressor T-cell ratios in early-onset forms of periodontal disease. J Periodont Res24:161-164.
44.
Komiyama K., Hirsch HZ, Moro I., Umemura S., Mestecky J. (1988). HNK-1+ (Leu-7) cells and natural killer cells activity in inflamed human gingival tissue. J Oral Pathol17:118-123.
45.
Kopp W. ( 1988). Density and localization of lymphocytes with natural-killer (NK) cell activity in periodontal biopsy specimens from patients with severe periodontitis. J Clin Periodontol15:595-600.
46.
Liljenberg B., Lindhe J., Berglundh T., DahlJn G., Johnsson R. (1994) Some microbiological, histopathological and immunohistochemical characteristics of progressive periodontal disease. J Clin Periodontol21:720-727.
47.
Lindemann RA (1988). Bacterial activation of human natural killer cells: role of cell surface lipopolysaccharide. Infect Immun56:1301-1308.
48.
Lindemann RA, Miyasaki KT, Wolinsky LE (1988). Induction of activated lymphocyte killing by bacteria associated with periodontal disease. J Dent Res67:846-850.
49.
Lindemann RA, Kjeldsen M., Cabret M. (1995). Effect of whole oral bacteria and extracted lipopolysaccharides on peripheral blood leukocyte interleukin-2 receptor expression. J Periodont Res30:264-271.
50.
Lundqvist C., Hammarstrom ML (1993). T-cell receptor gamma delta-expressing intraepithelial lymphocytes are present in normal and chronically inflamed human gingiva. Immunol79:38-45.
51.
Lundqvist C., Baranov V., Teglund S., Hammarstrom S., Hammarstrom ML (1994). Cytokine profile and ultra-structure of intraepithelial gamma delta T cells in chronically inflamed human gingiva suggest a cytotoxic effector function. J Immunol153:2302-2312.
52.
Maggi E., Del Prete GF, Macchia D., Parronchi P., Tiri A., Chretien I., et al. (1988). Profiles of lymphokine activities and helper function for IgE in human T cell clones. Eur J Immunol18:1045-1054.
53.
Mahanonda R., Seymour GJ, Powell LW, Good MF, Halliday JW (1989). Limit dilution analysis of peripheral blood T lymphocytes specific to periodontopathic bacteria. Clin Exp Immunol75:245-251.
54.
Mahanonda R. Seymour GJ, Powell LW, Good MF, Halliday IW (1991). Effect of initial treatment of chronic inflammatory periodontal disease on the frequency of peripheral blood T-lymphocytes specific to periodontopathic bacteria. Oral Microbiol Immunol6:221-227.
55.
Malberg K. Molle A., Streuer D., Gangler P. (1992). Determination of lymphocyte populations and subpopulations extracted from chronically inflamed human periodontal tissues. I Clin Periodontol19:155-158.
56.
Manhart SS, Reinhardt RA, Payne JB, Seymour GJ, Gemmell E., Dyer JK, et al. (1994). Gingival cell IL-2 and IL-4 in early-onset periodontitis. J Periodontol65:807-813.
57.
Mathur A., Michalowicz B., Yang C., Aeppli D. (1995). Influence of periodontal bacteria and disease status on Vβ expression in T cells. J Periodont Res30:369-373.
58.
McAnulty K., Stone R., Hastings G., Clagett J., Engel D. (1985). Immunoregulation in severe generalized periodontitis. Clin Immunol Immunopathol34:84-93.
59.
McFarlane CG, Reynolds JJ, Meikle MC (1990). The release of interleukin-1 beta, tumor necrosis factor-alpha and interferon-gamma by cultured peripheral blood mononuclear cells from patients with periodontitis. J Periodont Res25:207-214.
60.
Meng HX, Zheng LF (1989). T cells and T-cell subsets in periodontal diseases. J Periodont Res24:121-126.
61.
Modeer T., Dahllof G., Axio E., Sundqvist K. (1990). Subpopulations of lymphocytes in connective tissue from adolescents with periodontal disease. Acta Odontol Scand48:153-159.
62.
Mokyr MB, Rubin R., Newell KA, Prokhorova A., Bluestone JA (1993). Involvement of TCR-Vβ8.3+ cells in the cure of mice bearing a large MOPC-315 tumor by low dose melphalan. J Immunol151:4838-4846.
63.
Mosmann TR, Coffman RL (1989). TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol7:145-173.
64.
Mosmann TR, Cherwinski H., Bond MW, Giedlin MA, Coffman R. (1986). Two types of murine helper T-cell clones. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol136:2348-2357.
65.
Nagai A., Takahashi K., Sato N., Matsuo Y., Minowada J., Kurihara H., et al. (1993). Abnormal proportion of gamma delta T cells in peripheral blood is frequently detected in patients with periodontal disease. J Periodontol64:963-967.
66.
Nagasawa T., Nitta H., Watanabe H., Ishikawa I. (1995). Reduced CD8+ peripheral blood T lymphocytes in rapidly progressive periodontitis. Arch Oral Biol40:605-608.
67.
Nakajima T., Yamazaki K., Hara K. ( 1996). Biased T cell receptor V gene usage in tissues with periodontal disease. J Periodont Res31:2-10.
68.
Okada H. (1991). Phenotypic and functional characterizaton of peripheral blood T cells in adult periodontitis. J Periodont Res26(3 Pt 2):289-292.
69.
Okada H., Kassai Y., Kida T. ( 1984). T lymphocyte subsets in the inflamed gingiva of human adult periodontitis. J Periodont Res19:595-598.
70.
Osterberg SK, Page RC, Sims T., Wilde G. (1983). Blastogenic responsiveness of peripheral blood mononuclear cells from individuals with various forms of periodontal disease and effects of treatment. J Clin Periodontol10:72-88.
Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chretien I., Abrams J., et al. (1988). Simultaneous production of IL-2, IL-4 and IFN-gamma by activated human CD4+ and CD8+ T-cell clones. J Immunol141:849-855.
73.
Peppoloni S., Nencioni L., Di Tommaso A., Tagliabue A., Parronchi P., Romagnani S., et al. (1991). Lymphokine secretion and cytotoxic activity of human CD4+ T-cell clones against Bordetella pertussis. Infect Immun59:3768-3773.
74.
Prabhu A., Michalowicz BS, Mathur A. (1996). Detection of local and systemic cytokines in adult periodontitis. J Periodontol67:515-522.
75.
Reinhardt RA, Bolton RW, McDonald TL, DuBois LM, Kaldahl WB (1988a). In situ lymphocyte subpopulations from active versus stable periodontal sites. J Periodontol59:656-670.
76.
Reinhardt RA, McDonald TL, Bolton RW, DuBois LM, Feely DE, Kaldahl WB (1988b). In situ activated T lymphocytes in active versus stable periodontal lesions. J Periodont Res23:295-302.
77.
Reme T., Portier M., Frayssinouf F., Combe B., Miossec P., Favier F., et al. (1990). T cell receptor expression and activation of synovial lymphocyte subsets in patients with rheumatoid arthritis. Phenotyping of multiple synovial sites. Arthr Rheum33:485-492.
78.
Romagnani S. (1991). Human TH1 and TH2 cells: doubt no more. Immunol Today12:256-257.
79.
Romagnani S. (1994). Lymphokine production by human T cells in disease states. Ann Rev Immunol12:227-257.
80.
Rozzo SJ, Drake CG, Chiang B.-L, Gershwin ME, Kotzin BL (1994). Evidence for polyclonal T cell activation in murine models of systemic lupus erythematosus. J Immunol153:1340-1351.
81.
Seymour GJ, Horwood BW, Aaskov J., Powell RN (1984). Natural killer (NK) cell activity against human gingival fibroblasts exposed to dental plaque extracts. J Periodontol55:289-293.
82.
Seymour GJ, Cole KL, Powell RN, Lewins E., Cripps AW, Clancy RL (1985). Interleukin-2 production and bone-resorption activity in vitro by unstimulated lymphocytes extracted from chronically-inflamed human periodontal tissues. Arch Oral Biol30:481-484.
83.
Seymour GJ, Boyatzis S., Powell RN (1986). The autologous mixed lymphocyte reaction (AMLR) as a possible indicator of immunoregulation in chronic inflammatory periodontal disease (review). J Clin Periodontol13:639-645.
84.
Shenker BJ, Vitale L., King C. ( 1995). Induction of human T cells that coexpress CD4 and CD8 by an immunomodulatory protein produced by Actinobacilus actinomycetemcomitans. Cellular Immunol164:36-46.
85.
Stashenko P., Resmini LM, Haffajee AD, Socransky SS (1985). Helper ana suppressor T-cells in periodontal disease. J Periodont Res20:515-521.
86.
Stefanski H., Mathur A. (1996). Decreased expression and function of Vβ6+ and Vβ14+ T cells is associated with decreased Th 1 cytokine production in mice with plasma cell tumors. Tumori82:1-4.
87.
Stoufi ED, Taubman MA, Ebersole JL, Smith DJ, Stashenko PP (1987). Phenotypic analyses of mononuclear cells recovered from healthy and diseased human periodontal tissues. J Clin Immunol7:235-245.
88.
Suzuki JB, Pesk SK, Falkler WA (1984). Immunologic profiles of juvenile periodontitis. I. Lymphoblastogenesis and the autologous mixed lymphocyte reaction. I Periodontol55:453-460.
89.
Suzuki JB, Risom L., Falkler WA Jr, Collison C., Bowers G. (1985). Effect of periodontal therapy on spontaneous lymphocyte response and neutrophil chemotaxis in localized and generalized juvenile periodontitis patients. J Clin Periodontol12:124-134.
90.
Takahashi K., Takashiba S., Nagai A., Takigawa M., Myoukai F., Kurihara H., et al. (1994). Assessment of interleukin-6 in the pathogenesis of periodontal disease. J Periodontol65:147-153.
91.
Takahashi K., Nagai A., Satoh N., Kurihara H., Murayama Y. (1995). Studies on the phenotypic and functional characterization of peripheral blood lymphocytes from patients with early-onset periodontitis. J Periodontol66:391-396.
92.
Takeuchi Y., Yoshie H., Hara K. ( 1991). Expression of interleukin-2 receptor and HLA-DR on lymphocyte subsets of gingival crevicular fluid in patients with periodontitis. J Periodont Res26:502-510.
93.
Taubman MA, Stoufi ED, Ebersole JL, Smith DJ (1984). Phenotype studies of cells from periodontal tissues. J Periodont Res19:587-590.
94.
Taubman MA, Eastcott JW, Shimauchi H., Takeichi O., Smith DJ (1994). Modulatory role of T lymphocytes in periodontal inflammation. In: Molecular pathogenesis of periodontal disease. Genco R, Hamada S, Lehner T, McGhee J, Mergenhagen S, editors. Washington, DC: ASM Press, pp. 147-158.
95.
Tew JG, Burmeister JA, Palcanis KG, Ranney RR (1983). Spontaneous lymphocyte proliferation and periodontal status of young adults. J Periodont Res18:534-540.
96.
Tsicopoulos A., Hamid Q., Varney V., Ying S., Moqbel R., Durham SR, et al. (1992). Preferential messenger RNA expression of Thl-type cells (IFN-gamma+, IL-2+) in classical delayed type (tuberculin) hypersensitivity reactions in human skin. J Immunol148:2058-2061.
97.
Wassenaar A., Reinhardus C., Thepen T., Abraham-lnpijn L., Kievits F. (1995). Cloning, characterization, and antigen specificity of T-lymphocyte subsets extracted from gingival tissue of chronic adult periodontitis patients. Infect Immun63:2147-2153.
98.
Wierenga EA, Snoek M., deGroot C., Chretien I., Bos JD, Jansen HM, et al. (1990). Evidence for compartmentalization of functional subsets of CD4+ T lymphocytes in atopic patients. J Immunol144:4651-4656.
99.
Wynne SE, Walsh LJ, Seymour GJ, Powell RN (1986). In situ demonstration of natural killer (NK) cells in human gingival tissue. J Periodontol57:699-702. Yamazaki K., Nakajima T., Aoyagi T., Hara K. ( 1993). Immunohistological analysis of memory T lymphocytes and activated B lymphocytes in tissues with periodontal disease. J Periodont Res28:324-334. Yamazaki K., Nakajima T., Gemmell E., Polak B., Seymour GJ, Hara K. (1994). IL-4- and IL-6-producing cells in human periodontal disease tissue. J Oral Pathol Med23:347-353.
100.
Yamazaki K., Nakajima T., Hara K. ( 1995). Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease. Clin Exp Immunol99:384-391.
101.
Zadeh HH, Kreutzer DL (1996). Evidence for involvement of superantigens in human periodontal diseases: skewed expression of T cell receptor variable regions by gingival T cells. Oral Microbiol Immunol11:88-95. Zafiropoulos GG, Flores-de-Jacoby L., Schoop B., Havemann K., Heymanns J. (1990). Flow-cytometric analysis of lymphocyte subsets in patients with advanced periodontitis. J Clin Periodontol17:636-641. Zappa U., Reinking-Zappa M., Graf H., Espeland M. (1991). Cell populations and episodic periodontal attachment loss in humans. J Clin Periodontol18:508-515.
