In recent years, the phenotypic characterization of T cell subsets has given way to a functional dichotomy based essentially on their cytokine profiles. In this context, the CD4+ helper T cell subset has been shown to consist of two types, termed Th1 and Th2. In general, Th1 cells produce interleukin (IL)-2 and interferon (IFN)-gamma, while Th2 cells characteristicaly produce IL-4, IL-5, and IL-6. The major function of the Th1 subset is to mediate delayed-type hypersensitivity reactions and their secondary function is suppression of B cell activity. In contrast, the major function of the Th2 subset is to provide B cell help, while their secondary function is cell-mediated immune suppression. A similar dichotomy has also been described for CD8+ T cells. The role that these functional T cell subsets and their cytokines play in terms of their protective and nonprotective outcomes in a variety of infectious and oral diseases is reviewed.
Angelini, S.M., A.C. Trevino, and M.J. Novak: Mechanisms of Neutrophil Immobilization by Membrane Vesicles of Porphyromonas gingivalis. J. Dent. Res. 73:347(Abstr.) ( 1961).
3.
Attstrom, R. and J. Egelberg: Emigration of Blood Neutrophils and Monocytes into the Gingival Crevice. J. Periodont. Res. 5:48-55 (1970).
4.
Attstrom, R.: Studies on Neutrophil Polymorphonuclear Leukocytes at the Dento-Gingival Junction in Gingival Health and Disease. J. Periodont. Res. Suppl. 8:1-15 (1971).
5.
Audibert, F.M. and L.D. Lise: Adjuvants: Current Status, Clinical Perspectives and Future Prospects. Immunol. Today14:281-284 (1993).
6.
Balkwill, F.R. and F. Burke: The Cytokine Network. Immunol. Today9:299-304 (1989).
7.
Bancroft, G.J.: The Role of Natural Killer Cells in Innate Resistance to Infection. Curr. Opin. Immunol. 5:503-510 (1993).
8.
Bischoff, S.C., T. Brunner, A.L. De Week, and C.A. Dahinden: Interleukin 5 Modifies Histamine Release and Leukotriene Generation by Human Basophils in Response to Diverse Agonists. J. Exp. Med. 172:1577-1582 (1990).
9.
Bloom, B.R., P. Salgame, and B. Diamond: Revisiting and Revising Suppressor T Cells. Immunol. Today13:131-136 (1992).
10.
Bonnefoy, J.Y., M.C. Denoroy, O. Guillot, C.L. Martens, and J. Banchereau: Activation of Normal Human B Cells Through Their Antigen Receptor Induces Membrane Expression of IL-1 α andSecretion of IL-1β. J. Immunol. 143:864-869 (1989).
11.
Callard, R.E. and S.H. Smith: Interleukin 2 and Low Molecular Weight B Cell Growth Factor are T Cell Replacing Factors for Different Subpopulations of Human B Cells. Eur. J. Immunol. 18:1635-1638 (1988 ).
12.
Cambier, J.C. and J.T. Ransom: Molecular Mechanisms of Transmembrane Signaling in B Lymphocytes. Ann. Rev. Immunol. 5:175-199 (1987).
13.
Campbell, P.A.: Editorial Review. The Neutrophil, a Professional Killer of Bacteria May Be Controlled by T Cells. Clin. Exp. Immunol. 79:141-143 (1990).
14.
Chang, T.-L., C.M. Shea, S. Urioste, R.C. Thompson, W.H. Boom, and A.K. Abbas: Heterogeneity of Helper/ Inducer T Lymphocytes. III. Responses of IL-2- and IL-4-Producing (Thl and Th2) Clones to Antigens Presented.by Different Accessory Cells. J. Immunol. 145:2803-2808 (1990 ).
15.
Chatelain, R., K. Varkila, and R.L. Coffman: IL-4 Induces a Th2 Response in Leishmania major-Infected Mice. J. Immunol. 148(4):1182-1187 (1992 ).
16.
Chen, P.B., L.B. Davern, R. Schifferle, and J.J. Zambon: Protective Immunization Against Experimental Bacteroides (Porphyromonas) gingivalis Infection. Infect. Immun. 58:3394-3400 (1990).
17.
Chensue, S.W., P.D. Terebuh, K.S. Warmington, S.D. Hershey, H.L. Evanoff, S.L. Kunkel, and G.I. Higashi: Role of IL-4 and IFN-y in Schistosoma mansoni Egg-Induced Hypersensitivity Granuloma Formation. Orchestration, Relative Contribution and Relationship to Macrophage Function. J. Immunol. 148:900-906 (1992).
18.
Clagett, J.A. and R.C. Page: Insoluble Immune Complexes and Chronic Periodontal Diseases in Man and the Dog. Arch. Oral Biol. 23:153-165 (1978).
19.
Clerici, M. and G.M. Shearer: A TH1→TH2 Switch is a Critical Step in the Etiology of HIV Infection. Immunol. Today14:107-111 (1993).
20.
Cocks, B.G., R. de Waal Malefyt, J.P. Galizzi, J.E. de Vries, and G. Averas: IL-13 Induces Proliferation and Differentiation of Human B Cells Activated by the CD40 Ligand. Int. Immunol. 5(6):657-663 (1993).
21.
Coffman, R.L. and J. Carty: A T Cell Activity that Enhances Polyclonal IgE Production and its Inhibition by Interferon-Gamma. J. Immunol. 136:949-954 (1986).
22.
Coffman, R.L., J. Ohara, M.W. Bond, J. Carty, A. Zlotnik, and W.E. Paul: B Cell Stimulatory Factor-1 Enhances the IgE Response of Lipopolysaccharide-Activated B Cells. J. Immunol. 136:4538-4541 (1986 ).
23.
Coffman, R.L., K. Varkila, P. Scott, and R. Chatelain: Role of Cytokines in the Differentiation of CD4+ T-Cell Subsets In Vivo. Immunol. Rev. 123:189-207 (1991).
24.
Cole, K.C., G.J. Seymour, and R.N. Powell: Phenotypic and Functional Analysis of T Cells Extracted from Chronically Inflamed Human Periodontal Tissues. J. Periodontol. 58:569-573 (1987).
25.
Cox, F.E.G. and F.Y. Liew: T-Cell Subsets and Cytokines in Parasitic Infections. Immunol. Today13:445-448 (1992).
26.
Cutler, C.W., J.R. Kalmar, and R.R. Arnold: Phagocytosis of virulent Porphyromonas gingivalis by Human Polymorphonuclear Leukocytes Requires Specific Immunoglobulin G. Infect. Immun. 59:2097-2104 (1991).
27.
Czaja, M.J., F.R. Weiner, K.C. Flanders, M.A. Giambrone, R. Wind, L. Biempica, and M.A. Zem: In Vitro and In Vivo Association of Transforming Growth Factor-Beta 1 with Hepatic Fibrosis. J. Cell. Biol.108:2477-2482 (1989).
28.
Czuprynski, C.J., P.M. Henson, and P.A. Campbell: Enhanced Accumulation of Inflammatory Neutrophils and Macrophages Mediated by Transfer of T Cells from Mice Immunized with Listeria monocytogenes. J. Immunol. 134:3499-3454 (1985 ).
29.
De Kossodo, S. and G.E. Grau: Profiles of Cytokine Production in Relation with Susceptibility to Cerebral Malaria. J. Immunol. 151:4811-4820 (1993 ).
30.
Del Prete, G.F., M. De Carli, C. Mastromauro, R. Biagiotti, D. Macchia, P. Falagiani, M. Ricci, and S. Romagnani: Purified Protein Derivative of Mycobacterium tuberculosis and Excretory-Secretory Antigen(s) of Toxacara canis Expand In Vitro Human T Cells with Stable and Opposite (Type 1 T Helper or Type 2 T Helper) Profile of Cytokine Production. J. Clin. Invest. 88(1):346-350 (1991a).
31.
Del Prete, G.F., M. De Carli, M. Ricci, and S. Romagnani: Helper Activity for Immunoglobulin Synthesis of T Helper Type 1 (Th 1 ) and Th2 Human T Cell Clones: The Help of Th1 Clones Is Limited by Their Cytolytic Capacity. J. Exp. Med. 174(4):809-813 (1991b).
32.
Del Prete, G., M. De Carli, F. Almerigogna, M.G. Giudizi, R. Biagiotti, and S. Romagnani: 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. Immunol. 150(2):353-360 (1993).
33.
Del Prete, G., E. Maggi, P. Parronchi, I. Chretien, A. Tiri, D. Macchia, M. Ricci, J. Banchereau, J. De Vries, and S. Romagnani: IL-4 Is an Essential Factor for the IgE Synthesis Induced In Vitro by Human T Cell Clones and Their Supernatants. J. Immunol. 140:4193-4198 (1988).
34.
Denburg, J.A., J.E. Silver, and J.S. Abrams: Interleukin-5 Is a Human Basophilipoietin: Induction of Histamine Content and Basophilic Differentiation of HL-60 Cells and of Peripheral Blood Basophil-Eosinophil Progenitors. Blood77:1462-1468 (1991 ).
35.
De Vries, J.E., J. Punnonen, B.G. Cocks, and G. Aversa: The Role of T/B Cell Interactions and Cytokines in the Regulation of Human IgE Synthesis. Semin. Immunol. 5:431-439 (1993).
36.
De Waal Malefyt, R., H. Yssel, and J.E. de Vries: Direct Effects of IL-10 on Subsets of Human CD4+ T Cell Clones and Resting T Cells. Specific Inhibition of IL-2 Production and Proliferation. J. Immunol. 150(11): 4754-4765 (1993).
37.
De Waal Malefyt, R., H. Yssel, M.-G. Roncarolo, H. Spits, and J.E. de Vries: Interleukin-10. Curr. Opin. Immunol. 4:314-320( 1992).
38.
Dewhirst, F.E., P.P. Stashenko, J.E. Mole, and T. Tsurumachi: Purification and Partial Sequence of Human Osteoclast-Activating Factor: Identity with Interleukin-1. J. Immunol. 135:2562-2568 (1985).
39.
Dinarello, C.A.: The Biology of Interleukin 1 and Comparison to Tumor Necrosis Factor. Immunol. Lett. 16:227-232 (1987).
40.
Ding, L., P.S. Linsley, L.-Y. Huang, R.N. Germain, and E.M. Shevach: IL-10 Inhibits Macrophage Costimulatory Activity by Selectively Inhibiting the Up-Regulation of B7 Expression. J. Immunol. 151:1224-1234 (1993).
41.
Ding, L. and E.M. Shevach: IL-10 Inhibits Mitogen-Induced T Cell Proliferation by Selectively Inhibiting Macrophage Costimulatory Function. J. Immunol. 148:3133-3139 (1992).
42.
Doherty, T.M. and R.L. Coffman: Leishmania Antigens Presented by GM-CSF-Derived Macrophages Protect Susceptible Mice Against Challenge with Leishmania major. J. Immunol. 150:5476-5483 (1993).
43.
Ebersole, J.L., M.A. Taubman, and D.M. Smith: Gingival Crevicular Fluid Antibody to Oral Microorganisms. J. Periodont. Res. 20:349-356 (1985).
44.
Else, K.J., L. Hultner, and R.K. Grencis: Modulation of Cytokine Production and Response Phenotypes in Murine Trichuriasis. Parasite Immunol. 14(4):441-449 (1992).
45.
Else, K.J. and R.K. Grencis: Cellular Immune Responses to the Murine Nematode Parasite Trichuris muris. I. Differential Cytokine Production during Acute or Chronic Infection. Immunology72(4):508-513 (1991).
46.
Evans, R.T., B. Klausen, H.T. Sojar, G.S. Bedi, C. Sfintescu, N.S. Ramamurthy, L.M. Golub, and R.J. Genco: Immunization with Porphyromonas (Bacteroides) gingivalis Fimbriae Protects Against Periodontal Destruction. Infect. Immun. 60:2926-2935 (1992).
47.
Fabry, Z., M. Sandor, T.F. Gajewski, J.A. Herlein, M.M. Waldschmidt, R.G. Lynch, and M.N. Hart: Differential Activation of Th1 and Th2 CD4+ Cells by Murine Brain Microvessel Endothelial Cells and Smooth Muscle/Pericytes. J. Immunol. 151:38-47 (1993).
48.
Finkelman, F.D., I.M. Katona, T.R. Mosmann, and R.L. Coffman: IFN-y Regulates the Isotypes of Ig Secreted during In Vivo Humoral Immune Responses. J. Immunol. 140:1022-1027 (1988 ).
49.
Fiorentino, D.F., A. Zlotnik, P. Vieira, T.R. Mosmann, M. Howard, K.W. Moore, and A. O'Garra: IL-10 Acts on the Antigen-Presenting Cell to Inhibit Cytokine Production by Th1 Cells. J. Immunol. 146(10):3444-3451 (1991).
50.
Flores Villanueva, P.O., S.M. Chikunguwo, T.S. Harris, and M.J. Stadecker: Role of IL-10 on Antigen-Presenting Cell Function for Schistosomal Egg-Specific Monoclonal T Helper Cell Responses In Vitro and In Vivo. J. Immunol. 151:3192-3198 (1993 ).
51.
Freedman, A.S., G. Freeman, J. Whitman, J. Segil, J. Daley, and L.M. Nadler: Preexposure of Human B cells to Recombinant IL-1 Enhances Subsequent Proliferation. J. Immunol. 141:3398-3404 (1988 ).
52.
Fujihashi, K., Y. Kono, M. Yamamoto, J.R. McGhee, K. Beagley, W.K. Aicher, and H. Kiyono: Interleukin Production by Gingival Mononuclear Cells Isolated from Adult Periodontitis Patients. J. Dent. Res. 70:550 (Abstr. 2269) (1991).
53.
Fujihashi, K., M. Yamamoto, J.R. McGhee, and H. Kiyono: Type 1/Type 2 Cytokine Production by CD4+ T Cells in Adult Periodontitis. J. Dent. Res. 73:204 (Abstr. 818) (1994).
54.
Gascoigne, N.R.J.: Interactions of the T Cell Receptor with Bacterial Superantigens. Semin. Immunol. 5:13-21 (1993).
55.
Gazzinelli, R.T., F.T. Hakim, S. Hieny, G.M. Shearer, and A. Sher: Synergistic Role of CD4+ and CD8+ T Lymphocytes in IFN-gamma Production and Protective Immunity Induced by an Attenuated Toxoplasma gondii Vaccine. J. Immunol. 146(1):286-292 (1991).
56.
Gazzinelli, R.T., M. Makino, S.K. Chattopadhyay, C.M. Snapper, A. Sher, A.W. Hugin, and H.C. Morse: CD4+ Subset Regulation in Viral Infection. Preferential Activation of Th2 Cells during Progression of Retrovirus-Induced Immunodeficiency in Mice. J. Immunol. 148(1):182-188 (1992).
57.
Gemmell, E. and G.J. Seymour: Modulation of Immune Responses to Periodontal Bacteria. Curr. Opin. Periodont. 2nd ed. 28-38 (1994).
58.
Genco, R.J., P.A. Mashimo, G. Krygier, and S.A. Ellison: Antibody-Mediated Effects on the Periodontium. J. Periodontol. 45:330-337 (1974).
59.
Genco, R.J. and J. Slots: Host Responses in Periodontal Diseases. J. Dent. Res. 63:441-451 (1984).
60.
Genco, R.J., J.J. Zambon, and L.A. Christersson: The Origin of Periodontal Infections. Adv. Dent. Res. 2:245-259 (1988).
61.
Germann, T., M.K. Gately, D.S. Schoenhaut, M. Lohoff, F. Mattner, S. Fischer, S.C. Jin, E. Schmitt, and E. Rude: Interleukin-12/T Cell Stimulating Factor, a Cytokine with Multiple Effects of T Helper Type 1 (Th1) but not on Th2 Cells. Eur. J. Immunol. 23(8):1762-1770(1993).
62.
Ghezzi, P. and C.A. Dinarello: IL-1 Induces IL-1. III. Specific Inhibition of IL-1 Production by IFN-y. J. Immunol. 140:4238-4244 (1988 ).
63.
Graham, B.S., G.S. Henderson, Y.-W. Tang, X. Lu, K.M. Neuzil, and D.G. Colley: Priming Immunization Determines T Helper Cytokine mRNA Expression Patterns in Lungs of Mice Challenged with Respiratory Syncytial Virus. J. Immunol. 151:2032-2040 (1993 ).
64.
Gregory, S.H. and E.J. Wing: IFN-γ Inhibits the Replication of Listeria monocytogenes in Hepatocytes. J. Immunol. 151:1401-1409 (1993 ).
65.
Hamilton, T.A. and D.O. Adams: Molecular Mechanisms of Signal Transduction in Macrophages. Immunol. Today8:151-158 (1987).
66.
Heinzel, F.P., D.S. Schoenhaut, R.M. Rerko, L.E. Rosser, and M.K. Gately: Recombinant Interleukin 12 Cures Mice Infected with Leishmania major. J. Exp. Med. 177(5):1505-1509 (1993).
67.
Honig, J., C. Rordorf-Adam, C. Siegmund, W. Wiedemann, and F. Erard: Interleukin-1 Beta (IL-1β) Concentration in Gingival Tissue from Periodontitis Patients and Healthy Control Subjects. J. Periodont. Res. 24:362-367 (1989).
68.
Howard, M. and A. O'Garra: Biological Properties of Interleukin 10. Immunol. Today13:198-200 (1992).
69.
Howard, M., A. O'Garra, H. Ishida, R. de Waal Malefyt, and J. de Vries: Biological Properties of Interleukin 10. J. Clin. Immunol. 12:239-247 (1992).
70.
Inoue, T., Y. Asano, S. Matsuoka, M. Furutani-Seiki, S. Aizawa, H. Nishimura, T. Shirai, and T. Tada: Distinction of Mouse CD8+ Suppressor Effector T Cell Clones from Cytotoxic T Cell Clones by Cytokine Production and CD45 Isoforms. J. Immunol. 150(6):2121-2128 (1993).
71.
Jabara, H.H., S.M. Fu, R.S. Geha, and D. Vercelli: CD40 and IgE: Synergism between Anti-CD40 Monoclonal Antibody and Interleukin 4 in the Induction of IgE Synthesis by Highly Purified Human B Cells. J. Exp. Med. 172:1861-1864 (1990 ).
72.
James, S.L. and A. Sher: Cell-Mediated Immune Response to Schistosomiasis. Curr. Top. Microbiol. Immunol. 155:21-31 (1990).
Kamanga-Sollo, E.I.P., K. Rehder, B. Michalowicz, and A. Mathur: Expression of TCR Vβ Families in Patients with Periodontitis. J. Dent. Res. 73:203 (Abstr. 815) (1994).
75.
Karp, C.L., S.H. EI-Safi, T.A. Wynn, M.M.H. Satti, A.M. Kordofani, F.A. Hashim, M. Hag-Ali, F.A. Neva, T.B. Nutman, and D.L. Sacks: In Vivo Cytokine Profiles in Patients with Kala-azar. Marked Elevation of both Interleukin-10 and Interferon-y. J. Clin. Invest.91:1644-1648 (1993).
76.
Kehri, J.H., L.M. Wakefield, A.B. Roberts, S.B. Jakowlew, M. Alvarez-Mon, R. Derynck, M.B. Sporn, and A.S. Panci: Production of Transforming Growth Factor Beta by Human T Lymphocytes and its Potential Role in the Regulation of T Cell Growth. J. Exp. Med. 163:1037-1050 (1986).
77.
Kelso, A.: Cytokines in Infectious Disease. Austr. Microbiol. 11:372-376 (1990).
78.
Kesavalu, L., J.L. Ebersole, R.L. Machen, and S.C. Holt: Porphyromonas gingivalis Virulence in Mice: Induction of Immunity to Bacterial Components. Infect. Immun. 60:1455-1464 (1992).
79.
Lane, H.C., H. Masur, L.C. Edgar, G. Whalen, A.H. Rook, and A.S. Fauci: Abnormalities of B Cell Activation and Immunoregulation in Patients with the Acquired Immunodeficiency Syndrome. N. Engl. J. Med. 309:453-458 (1983).
80.
Locksley, R.M. and P. Scott: Helper T Cell Subsets in Mouse Leishmaniasis Induction, Expansion and Effector Function. Immunol. Today12(3):A58-61 (1991).
81.
Lopatin, D.E. and E. Blackburn: Avidity and Titer of Immunoglobulin G Subclasses to Porphyromonas gingivalis in Adult Periodontitis Patients. Oral Microbiol. Immunol. 7:332-337 (1992).
82.
Lloyd, A.R. and J.J. Oppenheim: Poly's Lament: The Neglected Role of the Polymorphonuclear Neutrophil in the Afferent Limb of the Immune Response. Immunol. Today13:169-172 (1992).
83.
Lundgren, M., U. Persson, P. Larsson, C. Magnusson, C.I.E. Smith, L. Hammarstrom, and E. Severinson: Interleukin 4 Induces Synthesis of IgE and IgG4 in Human B Cells. Eur. J. Immunol. 19:1311-1315 (1989 ).
84.
MacFarlane, G.D., M.C. Herzberg, L.F. Wolff, and N.A. Hardie: Refractory Periodontitis Associated with Abnormal Polymorphonuclear Leukocyte Phagocytosis and Cigarette Smoking. J. Periodontol. 63:908-913 (1992).
85.
Mahanti, S., C.L. King, V. Kumaraswami, J. Regunathan, A. Maya, K. Jayaraman, J.S. Abrams, E.A. Ottesen, and T.B. Nutman: IL-4- and IL-5-Secreting Lymphocyte Populations Are Preferentially Stimulated by Parasite-Derived Antigens in Human Tissue Invasive Nematode Infections. J. Immunol. 151:3704-3711 (1993 ).
86.
Masada, M.P., R. Persson, J.S. Kenney, S.W. Lee, R.C. Page, and A.C. Allison: Measurement of Interleukin-1α and -1β in Gingival Crevicular Fluid: Implication for the Pathogenesis of Periodontal Disease. J. Periodont. Res. 25:156-163 (1990).
87.
Matsushima, K., A. Procopio, H. Abe, G. Scala, J.R. Ortaldo, and J.J. Oppenheim: Production of Interleukin 1 Activity by Normal Human Peripheral Blood B Lymphocytes. J. Immunol. 135:1132-1136 (1985 ).
88.
Mayrand, D. and S.C. Holt: Biology of Asaccharolytic Bacteroides Species. Microbiol. Revs. 2:134-152 (1988).
89.
Meghji, S., B. Henderson, and M. Wilson: High-Titer Antisera from Patients with Periodontal Disease Inhibit Bacterial Capsule-Induced Bone Breakdown. J. Periodont. Res. 28:115-121 (1993).
90.
Meikle, M.C., J.K. Heath, and J.J. Reynolds: Advances in Understanding Cell Interactions in Tissue Resorption. Relevance to the Pathogenesis of Periodontal Diseases and a New Hypothesis. J. Oral Pathol. 15:239-250 (1986).
91.
Micusan, V.V. and J. Thibodeau: Superantigens of Microbial Origin. Semin. Immunol. 5:3-11 (1993).
92.
Miyawaki, T., T. Suzuki, J.L. Butler, and M.D. Cooper: Interleukin-2 Effects on Human B Cells Activated In Vivo. J. Clin. Immunol. 7:277-287 (1987).
93.
Modlin, R.L. and T.B. Nutman: Type 2 Cytokines and Negative Immune Regulation in Human Infections. Curr. Opin. Immunol. 5:511-517 (1993).
Mosmann, T.R.: Cytokines: Is There Biological Meaning? Curr. Opin. Immunol. 3:311-314 (1991).
96.
Mosmann, T.R. and R.L. Coffman: TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties. Ann. Rev. Immunol. 7:145-173 (1989).
97.
Murayama, Y., A. Nagai, K. Okamura, H. Kurihara, Y. Nomura, S. Kokeguchi, and K. Kato: Serum Immunoglobulin G Antibody to Periodontal Bacteria. Adv. Dent. Res. 2:339-345 (1988).
98.
Naito, Y., K. Okuda, I. Takazoe, H. Watanabe, and I. Ishikawa: The Relationship between Serum IgG Levels to Sub-Gingival Gram-Negative Bacteria and Degree of Periodontal Destruction. J. Dent. Res. 64:1306-1310 (1985).
99.
Naor, D.: Short Analytical Review. A Different Outlook at the Phenotype-Function Relationships of T Cell Subpopulations: Fundamental and Clinical Implications. Clin. Immunol. Immunopath. 62:127-132 (1992).
100.
Ochi, A., K. Yuh, and K. Migita: Not Every Superantigen Induces Tolerance In Vivo. Semin. Immunol. 5:57-63 (1993).
101.
O'Garra, A., S. Umland, T. De France, and J. Christiansen: B-Cell Factors Are Pleiotropic. Immunol. Today9:45-54 (1988).
102.
O'Garra, A.: Peptide Regulatory Factors. Interleukins and the Immune System 1. Lancet1:943-946 (1988a).
103.
O'Garra, A.: Peptide Regulatory Factors. Interleukins and the Immune System 2. Lancet1:1003-1005 (1989b).
104.
Ogawa, T., Y. Kushumoto, S. Hamada, J.R. McGhee, and H. Kiyono: Bacteroides gingivalis-Specific Serum IgG and IgA Subclass Antibodies in Periodontal Disease. Clin. Exp. Immunol. 82:318-325 (1990).
105.
Okuda, K. and I. Takazoe: The Role of Bacteroides gingivalis in Periodontal Disease. Adv. Dent. Res. 2:260-268 (1988).
106.
Okuda, K., T. Kato, Y. Naito, Y. Kikuchi, and I. Takazoe: Susceptibility of Bacteroides gingivalis to Bactericidal Activity of Human Serum. J. Dent. Res. 65:1024-1027 (1986 ).
107.
Orme, I.M., A.D. Roberts, J.P. Griffin, and J.S. Abrams: Cytokine Secretion by CD4 T Lymphocytes Acquired in Response to Mycobacterium tuberculosis Infection. J. Immunol. 151(1):518-525 (1993).
108.
Page, R.C.: The Role of Inflammatory Mediators in the Pathogenesis of Periodontal Disease. J. Periodont. Res. 26:230-242 (1991).
109.
Parronchi, P., M. De Carli, R. Manetti, C. Simonelli, S. Sampognaro, M.P. Piccinni, D. Macchia, E. Maggi, G. Del-Prete, and S. Romagnani: IL-4 and IFN (Alpha and Gamma) Exert Opposite Regulatory Effects on the Development of Cytolytic Potential by Th1 or Th2 Human T Cell Clones. J. Immunol. 149(9):2977-2983 (1992 ).
110.
Pearlman, E., F.E. Hazlett, W.H. Boom, and J.W. Kazura: Induction of Murine T-Helper-Cell Responses to the Filarial Nematode Brugia malayi. Infect. Immun. 61(3):1105-1112 (1993).
111.
Persson, G.R., D. Engel, C. Whitney, R. Darveau, A. Weinberg, M. Brunsvold, and R.C. Page: Immunization against Porphorymonas gingivalis Inhibits Progression of Experimental Periodontitis in Nonhuman Primates. Infect. Immun. 62:1026-1031 (1994).
112.
Pfeilschifter, J.: Transforming Growth Factor-β. In: Growth Factors, Differentiation Factors, and Cytokines, pp. 56-64. ( Habenicht, A., Ed.) Springer-Verlag, Berlin (1990).
113.
Pilon, M., C. Williams-Miller, and D.S. Cox: Interleukin-2 Levels in Gingival Crevicular Fluid in Periodontitis. J. Dent. Res. 70:550 (Abstr. 2270) (1991).
114.
Platt, D., R.G. Crosby, and M.H. Dalbow: Evidence for the Presence of Immunoglobulins and Antibodies in Inflamed Periodontal Tissues. J. Periodontol. 41:215-222 (1970).
115.
Powrie, F. and R.L. Coffman: Cytokine Regulation of T-Cell Function: Potential for Therapeutic Intervention. Immunol. Today14:270-274 (1993).
116.
Punnonen, J., R. de Waal Malefyt, P. van Vlasselaer, J.-F. Gauchat, and J.E. de Vries: IL-10 and Viral IL-10 Prevent IL-4-Induced IgE Synthesis by Inhibiting the Accessory Cell Function of Monocytes. J. Immunol. 151:1280-1289 (1993).
117.
Reed, G.R. and P. Scott: T-Cell and Cytokine Responses in Leishmaniasis. Curr. Opin. Immunol. 5:524-531 (1993).
118.
Reinhardt, R.A., T.L. McDonald, R.W. Bolton, L.M. Dubois, and W.B. Kaldahl: IgG Subclasses in Gingival Crevicular Fluid from Active Vs. Stable Periodontal Sites. J. Periodontol. 60:44-50 (1989).
119.
Reinherz, E.L. and S.F. Schlossman: The Differentiation and Function of Human T Lymphocytes. Cell19:821-827 (1980).
120.
Reinherz, E.L.: A Molecular Basis for Thymic Selection: Regulation of T11 1 Induced Thymocyte Expansion by the T3-Ti Antigen/MHC Receptor Pathway. Immunol. Today6:75-79 (1985).
121.
Ribero de Jesus, A.M., R.P. Almeida, O. Bacellar, M.I. Arujo, C. Demeure, J.C. Bina, A.J. Dessein, and E.M. Carvalho: Correlation between Cell-Mediated Immunity and Degree of Infection in Subjects Living in an Endemic Area of Schistosomiasis. Eur. J. Immunol. 23:152-158 (1993).
122.
Röcken, M., K.M. Miiller, J.-H. Saurat, I. Miiller, J.A. Louis, J.-C. Cerottini, and C. Hauser: Central Role for TCR/CD3 Ligation in the Differentiation of CD4+ T Cells Toward a Th1 or Th2 Functional Phenotype. J. Immunol. 148:47-54 (1992a).
123.
Rocken, M., J.H. Saurat, and C. Hauser: A Common Precursor for CD4+ T Cells Producing IL-2 or IL-4. J. Immunol. 148:1031-1036 (1992 b).
124.
Romagnani, S.: Regulation and Deregulation of Human IgE Synthesis. Immunol. Today11:316-321 (1990).
125.
Romagnani, S.: Human TH1 and TH2 Subsets: Regulation of Differentiation and Role in Protection and Immunopathology. Int. Arch. Allergy Immunol. 98(4):279-285 (1992a).
126.
Romagnani, S.: Induction of TH1 and TH2 Responses: A Key Role for the "Natural" Immune Response? Immunol. Today13(10):379-381 (1992b).
127.
Rosa, F. and M. Fellows: Effect of Gamma-Interferon on MHC Antigens. Immunol. Today9:261-262 (1984).
128.
Rousset, F., E. Garcia, T. Defrance, C. Peronne, N. Vezzio, D.H. Hsu, R. Kastelein, K.W. Moore, and J. Banchereau: Interleukin 10 is a Potent Growth and Differentiation Factor for Activated Human B Lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 89(5):1890-1893 (1992).
129.
Schenk, K.: IgG, IgA and IgM Serum Antibodies Against Lipopolysaccharide from Bacteroides gingivalis in Periodontal Health and Disease. J. Periodont. Res. 20:368-377 (1985).
130.
Schenk, K. and T.E. Michaelsen: IgG Subclass Distribution of Serum Antibodies Against Lipopolysaccharide from Bacteroides gingivalis in Periodontal Health and Disease. Acta Pathol. Microbiol. Immunol. Scand. 95:41-46 (1987).
131.
Schroeder, H.E.: Transmigration and Infiltration of Leukocytes in Human Junctional Epithelium. Acta Odont. Scand. 17:6 (1973).
132.
Scott, P.: IFN-y Modulates the Early Development of Th1 and Th2 Responses in a Murine Model of Cutaneous Leishmaniasis. J. Immunol. 147:3149-3155 (1991).
133.
Scott, P.: Selective Differentiation of CD4+ T Helper Cell Subsets. Curr. Opin. Immunol. 5:391-397 (1993).
134.
Scott, P. and S.H.E. Kaufmann: The Role of T-Cell Subsets and Cytokines in the Regulation of Infection. Immunol. Today12:346-348 (1991).
135.
Seow, W.K., P.S. Bird, G.J. Seymour, and Y.H. Thong: Modulation of Human Neutrophil Adherence by Periodontopathic Bacteria: Reversal by Specific Monoclonal Antibodies. Int. Arch. Allergy Appl. Immunol. 90:24-30 (1989).
136.
Seymour, G.J.: Importance of the Host Response in the Periodontium. J. Clin. Periodontol. 18:421-426 (1991).
137.
Seymour, G.J.: Possible Mechanisms Involved in the Immunoregulation of Chronic Inflammatory Periodontal Disease. Invited Review. J. Dent. Res. 66:2-9 (1987).
138.
Seymour, G.J., E. Gemmell, R.A. Reinhardt, J. Eastcott, and M.A. Taubman: Immunopathogenesis of Chronic Inflammatory Periodontal Disease: Cellular and Molecular Mechanisms. J. Periodont. Res. 28:478-486 (1993).
139.
Sher, A., R.T. Gazzinelli, I.P.Oswald, M. Clerici, M. Kullberg, E.J. Pearce, J.A. Berzofsky, T.R. Mosmann, S.L. James, H.C. Morse, and G.M. Shearer: Role of T-Cell-Derived Cytokines in the Downregulation of Immune Responses in Parasitic and Retroviral Infection. Immunol. Rev. 127:181-204 (1992).
140.
Sieling, P.A., J.S. Abrams, M. Yamamura, P. Salgame, B.R. Bloom, T.H. Rea, and R.L. Modlin: Immunosuppressive Roles for IL-10 and IL-4 in Human Infection. J. Immunol. 150:5501-5510 (1993 ).
141.
Slots, J. and R.J. Genco: Black-Pigmented Bacteroides Species, Capnocytophaga Species, and Actinobacillus actinomycetemcomitans in Human Periodontal Disease: Virulence Factors in Colonization Survival and Tissue Destruction. J. Dent. Res. 63:412-421 (1984).
142.
Slots, J.: Subgingival Microflora and Periodontal Disease. J. Clin. Periodontol. 6:351-382 (1979).
143.
Snapper, C.M. and W.E. Paul: Interferon-y and B Cell Stimulatory Factor-1 Reciprocally Regulate Ig Isotype Production. Science236:944-947 (1987).
144.
Socransky, S.S., A.D. Haffajee, J.L. Dzink, and J.D. Hillman: Associations between Microbial Species in Subgingival Plaque Samples. Oral Microbiol. Immunol. 3:1-7 (1988).
145.
Sporn, M.B., A.B. Roberts, L.M. Wakefield, and B. De Crombrugghe: Some Recent Advances in the Chemistry and Biology of Transforming Growth Factor-Beta. J. Cell Biol. 105:1039-1045 (1987).
146.
Stashenko, P., P. Fujiyoshie, M.S. Obernesser, L. Prostak, A.D. Haffajee, and S.S. Socransky: Levels of Interleukin 1 Beta in Tissue from Sites of Active Periodontal Disease. J. Clin. Periodontol. 18:548-554 (1991).
147.
Stevenson, M.M. and M.F. Tam: Differential Induction of Helper T Cell Subsets during Blood-Stage Plasmodium chabaudi AS Infection in Resistant and Susceptible Mice. Clin. Exp. Immunol. 92:77-83 (1993).
148.
Street, N.E. and T.R. Mosmann: Functional Diversity of T Lymphocytes Due To Secretion of Different Cytokine Patterns. FASEB J. 5:171-177 (1991).
149.
Subauste, C.S. and J.S. Remington: Immunity to Toxoplasma gondii. Curr. Opin. Immunol. 5:532-537 (1993).
150.
Sunderkotter, C., M. Kunz, K. Steinbrink, G. Meinardus-Hager, M. Goebeler, H. Bildau, and C. Sorg: Resistance of Mice to Experimental Leishmaniasis Is Associated with More Rapid Appearance of Mature Macrophages In Vitro and In Vivo. J. Immunol. 151(9):4891-4901 (1993 ).
151.
Surcel, H.M., M. Troye-Blomberg, S. Paulie, G. Andersson, C. Moreno, G. Pasvol, and J. Ivanyi: Thl/Th2 Profiles in Tuberculosis Based on the Proliferation and Cytokine Response of Blood Lymphocytes to Mycobacterial Antigens. Immunology81:171-176 (1994).
152.
Suzuki, J.B., S.A. Martin, J.W. Vincent, and W.A. Falkler, Jr.: Local and Systemic Production of Immunoglobulins to Periodontopathogens in Periodontal Disease. J. Periodont. Res. 19:599-603 (1984).
153.
Swain, S.L.: Lymphokines and the Immune Response: The Central Role of Interleukin-2. Curr. Opin. Immunol. 3:304-310 (1991).
154.
Syed, S.A. and W.J. Loesche: Bacteriology of Human Experimental Gingivitis: Effects of Plaque Age. Infect. Immun. 21:821-829 (1978).
155.
Tanner, A.C.R., S.S. Socransky, and J.M. Goodson: Microbiota of Periodontal Pockets Losing Crestal Alveolar Bone. J. Periodont. Res. 19:279-291 (1984).
156.
Tanner, A.C.R., C. Haffer, G.T. Bratthall, R.A. Visconti, and S.S. Socransky: A Study of the Bacteria Associated with Advancing Periodontitis in Man. J. Clin. Periodont. 6:278-307 (1979).
157.
Taubman, M.A., E.D. Stoufi, J.L. Ebersole, and D.J. Smith: Phenotypic Studies of Cells from Periodontal Disease Tissue. J. Periodont. Res. 19:587-590 (1984).
158.
Taylor-Robinson, A.W. and R.S. Phillips: Functional Characterization of Protective CD4+ T-Cell Clones Reactive to the Murine Malaria Parasite Plasmodium chabaudi. Immunology77(1):99-105 (1992).
159.
Tovey, M.G., J. Content, I. Gresser, J. Gugenheim, B. Blanchard, J. Guymarho, P. Poupart, M. Gigon, A. Shaw, and W. Fiers: Genes for IFN-β-2 (IL-6), Tumor Necrosis Factor, and IL-1 are Expressed at High Levels in the Organs of Normal Individuals. J. Immunol. 141:3106-3110 (1988).
160.
Trinchieri, G.: Interleukin-12 and Its Role in the Generation of TH1 Cells. Immunol. Today14:335-337 (1993).
161.
Trinchieri, G. and B. Perussia: Immune Interferon: A Pleiotropic Lymphokine with Multiple Effects. Immunol. Today6:131-136 (1985).
162.
Van Dyke, T.E., E. Bartholomew, R.J. Genco, J. Slots, and M.J. Levine: Inhibition of Neutrophil Chemotaxis by Soluble Bacterial Factors. J. Periodontol. 53:502-508 (1982).
163.
Van Dyke, T.E., M.A. Lester, and L. Shapira: The Role of the Host Response in Periodontal Disease Progression: Implications for Future Treatment Strategies. J. Periodontol.64(Suppl.):792-806 (1993).
164.
Van Snick, J. and R.P. Nordon: In: Growth Factors, Differentiation Factors, and Cytokines, pp. 163-176. (Habenicht, A., Ed.) Springer-Verlag, Berlin (1990).
165.
Vella, A.T. and E.J. Pearce: CD4+ Th2 Response Induced by Schistosoma mansoni Eggs Develops Rapidly, Through an Early, Transient, ThO-like Stage. J. Immunol. 148:2283-2290 (1992).
166.
Whitney, C., J. Ant, B. Moncla, B. Johnson, R.C. Page, and D. Engel: Serum Immunoglobulin G Antibody to Porphyromonas gingivalis in Rapidly Progressive Periodontitis: Titer, Avidity, and Subclass Distribution. Infect. Immun. 60:2194-2200 (1992 ).
167.
Wierenga, E.A., M. Snoek, C. de Groot, I. Chretien, J.D. Bos, H.M. Jansen, and M.L. Kapsenberg: Evidence of Compartmentalization of Functional Subsets of CD2+ Lymphocytes in Atopic Patients. J. Immunol. 144:4651-4656 (1990).
168.
Wilson, R.A.: Immunity and Immunoregulation in Helminth Infections. Curr. Opin. Immunol. 5:538-547 (1993).
169.
Wong, G.C. and S.C. Clark: Multiple Actions of Interleukin 6 within a Cytokine Network. Immunol. Today9:137-139 (1988).
170.
Wynne, S.E., L.J. Walsh, G.J. Seymour, and R.N. Powell: In Situ Demonstration of Natural Killer (NK) Cells in Human Gingival Tissue. J. Periodontol. 57:699-702 (1986).
171.
Xu, Y.H., J. Macedonia, A. Sher, E. Pearce, and A.W. Cheever: Dynamic Analysis of Splenic Th1 and Th2 Lymphocyte Functions in Mice Infected with Schistosoma japonicum. Infect. Immun. 59(9):2934-2940 (1991).
172.
Xu Amano, J., W.K. Aicher, T. Taguchi, H. Kiyono, and J.R. McGhee: Selective Induction of TH2 Cells in Murine Peyer's Patches by Oral Immunisation. Int. Immunol. 4(4):433-445 (1992).
173.
Xu Amano, J., H. Kiyono, R.J. Jackson, H.F. Staats, K. Fujihashi, P.D. Burrows, C.O. Elson, S. Pillai, and J.R. McGhee: Helper T Cell Subsets for Immunoglobulin A Responses: Oral Immunisation with Tetanus Toxoid and Cholera Toxin as Adjuvant Selectively Induces Th2 Cells in Mucosa-Associated Tissues. J. Exp. Med.178(4):1309-1320 (1993 ).
174.
Yamamura, M., X.-H. Wang, J.D. Ohmen, K. Uyemura, T.H. Rea, B.R. Bloom, and L. Modlin: Cytokine Patterns of Immunologically Mediated Tissue Damage. J. Immunol. 149:1470-1475 (1992 ).
175.
Yamashita, T. and D.L. Boros: IL-4 Influences IL-2 Production and Granulomatous Inflammation in Murine Schistosomiasis mansoni. J. Immunol. 149:3659-3664 (1992 ).
176.
Yamashita, K., J.W. Eastcott, M.A. Taubman, D.J. Smith, and D.S. Cox: Effect of Adoptive Transfer of a Cloned Actinobacillus actinomycetemcomitans - Specific T Helper Cells on Periodontal Disease. Infect. Immun. 59:1529-1534 (1991).
177.
Yamazaki, K., B. Polak, P.S. Bird, E. Gemmell, K. Hara, and G.J. Seymour: Effects of Periodontopathic Bacteria on IL-1 and IL-1 Inhibitor Production by Human Polymorphonuclear Neutrophils. Oral Microbiol. Immunol. 4:193-198 (1989).
178.
Yssel, H., K.E. Johnson, P.V. Schneider, J. Wideman, A. Terr, R. Kastelein, and J.E. de Vries: T-Cell Activation-Inducing Epitopes of the House Dust Mite Allergen Der p1. Proliferation and Lymphokine Production Patterns by Der pl-specific CD4+ T Cell Clones. J. Immunol. 148:738-745 (1992a).
179.
Yssel, H., R. De Waal Malefyt, M.G. Roncarolo, J.S. Abrams, R. Lahesmaa, H. Spits, and J.E. de Vries: IL-10 is Produced by Subsets of Human CD4+ T Cell Clones and Peripheral Blood T Cells. J. Immunol. 149(7):2378-2384 (1992b).
180.
Zadeh, H.H. and D. Kreutzer: Analysis of Gingival T Cell Subsets Suggests Expansion by Superantigens. J. Dent. Res.73:204 (Abstr. 817) (1994).
181.
Zhang, J.-H., A. Ferrante, A.-P. Arrigo, and J.-M. Dayer: Neutrophil Stimulation and Priming by Direct Contact with Activated Human T Lymphocytes. J. Immunol. 148:177-181 (1992).
182.
Zurawski, G. and J.E. de Vries: Interleukin 13, an Interleukin 4-like Cytokine That Acts on Monocytes and B Cells, but Not on T Cells. Immunol. Today15:19-26 (1994).
