• 1
    Kay, A. B., Ying, S., Varney, V., Gaga, M., Durham, S.R., Mogbel, R., Wardlaw, A. J. and Hamid, Q. A., Messenger RNA expression of the cytokine gene cluster interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects. J. Exp. Med. 1991. 173: 775778.
  • 2
    Mosmann, T. R. and Sad, S., The expanding universe of T cell subsets: Th1, Th2 and more. Immunol. Today 1996. 17: 142146.
  • 3
    Seder, R. A., Gazzinelli, R., Sher, A. and Paul, W. E., Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc. Natl. Acad. Sci. USA 1993. 90: 1018810192.
  • 4
    Jutel, M., Watanabe, T., Klunker, S., Akdis, M., Thomet, O. A. R., Malolepszy, J., Zak-Nejmarrk, T., Koga, R., Kobayashi, T., Blaser, K. and Akdis, A. C., Histamine regulates T cell and antibody responses by differential expression of H1 and H2 receptors. Nature 2001. 413: 420425.
  • 5
    Akdis, C. A. and Blaser, K., Mechanisms of interleukin-10-mediated immune suppression. Immunology 2001. 103: 131136.
  • 6
    Groux, H., O'Garra, A., Bigler, M., Rouleau, M., Antonenko, S., De Vries, J. E. and Roncarolo, M. G., A CD4+ T cell subset inhibits antigen-specific T cell responses and prevents colitis. Nature 1997. 389: 737742.
  • 7
    Akdis, C. A., Blesken, T., Akdis, M., Wüthrich, B. and Blaser, K., Role of IL-10 in specific immunotherapy. J. Clin. Invest. 1998. 102: 98106.
  • 8
    Medzhitov, R. and Janeway, C. A. J., Innate immunity: the virtues of a nonclonal system of recognition. Cell 1997. 91: 295298.
  • 9
    Takeda, K., Kaisho, T. and Akira, S., Toll-like receptors. Annu. Rev. Immunol. 2003. 21: 335376.
  • 10
    Krieg, A. M., Yi, A. K., Schorr, J. and Davis, H., The role of CpG oligonucleotides in DNA vaccines. Trends Microbiol. 1998. 6: 2327.
  • 11
    Raz, E., Tighe, H., Sati, Y., Corr, M., Dudler, J. A., Roman, M., Swain, S. L., Spiegelberg, H. L. and Carson, D. A., Preferential induction of Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc. Natl. Acad. Sci. USA 1996. 93: 51415145.
  • 12
    Kawai, T., Adachi, O., Ogawa, T., Takeda, K. and Akira, S., Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 1999. 11: 115122.
  • 13
    Sluss, H. K., A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila. Genes Dev. 1996. 10: 27452758.
  • 14
    Brightbill, H. D., Libraty, D. H., Krutzik, S. R., Yang, R. B., Belisle, J. T., Bleharski, J. L., Maitland, M., Norgard, M. V., Plevy, S. E., Smale, S. T., Brennan, P. J., Bloom, B. R., Godowski, P. J. and Modlin, R. L., Host defense mechanisms triggered by microbial lipoproteins through Toll-like receptors. Science 1999. 285: 732736.
  • 15
    Dérijard, B., Hibi, M., Wu, I.-H., Barret, T., Su, B., Deng, T., Karin, M. and Davis, R. J., JNK1: A protein kinase stimulated by UV lightand Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 1994. 76: 10251037.
  • 16
    Ogilvie, B. M., Reagin-like antibodies in rat infected with nematode parasite Nippostrongylus brasiliensis. Immunology 1967.12: 113131.
  • 17
    Finkelman, F. D., T help requirements for the generation of an in vivo IgE response: a late acting from of T cell help other than IL-4 is required for IgE but not IgG1 production. J. Immunol. 1989. 142: 403408.
  • 18
    Aziz, D. C., Hanna, Z. and Jolicoeur, P., Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature 1989. 338: 505508.
  • 19
    Coyle, J. A. and Tsuyuki, S., Th2 cells and cytokine networks in the allergic inflammation of the lung. Mediators Inflamm. 1995. 4: 239247.
  • 20
    Wynn, T. A., Eltoum, I., Oswald, I. P., Cheever, A. W. and Sher, A., Endogenous interleukin 12 (IL-12) regulates granuloma formation induced by eggs of Schistosoma mansoni and exogenous IL-12 both inhibits and prophylactically immunizes against egg pathology. J. Exp. Med. 1994. 179: 15511561.
  • 21
    Sing, A., Rost, D., Tvardovskaia, N., Roggenkamp, A., Wiedemann, A., Kirsching, C. J., Aepfelbacher, M. and Heesemann, J., Yersinia V-antigen exploits Toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression. J. Exp. Med. 2002. 196: 10091012.
  • 22
    Barton, G. M. and Medzhitov, R., Control of adaptive immune responses by Toll-like receptors. Curr. Opin. Immunol. 2002. 14: 380383.
  • 23
    Pulendran, B., Kumar, P., Cutler, C. W., Mohamadzaadeh, M., Van Dyke, T. and Banchereau, J., Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo. J. Immunol. 2001. 167: 50675076.
  • 24
    Hirschfeld, M., Weis, J. J., Toshchakov, V., Salkowski, C. A., Cody, M. J., Ward, D. C., Qureshi, N., Michalek, S. M. and Vogel, S. N., Signaling by Toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect. Immun. 2001. 69: 14771482.
  • 25
    Del Prete, G., Maggi, E., Paola, P., Ghretien, I., Tiri, A., Macchia, D., Banchereau, J., De Vries, J. and Romagnani, S., IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J. Immunol. 1988. 140: 41934198.
  • 26
    Punnonen, J., Aversa, G., Cocks, B. G., McKenzie, A. N. J., Menon, S., Zurawski, G., De Waal Malefyt, R. and De Vries, J. E., Interleukin 13 induces interleukin 4 independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc. Natl. Acad. Sci. USA 1993. 90: 37303734.
  • 27
    Akdis, C. A. and Blaser, K., Bypassing IgE and targeting T cells for specific immunotherapy of allergy. Trends Immunol. 2001. 22: 175178.
  • 28
    Punnonen, J., De Waal Malefyt, R., Van Vlasselaer, P., Gauchat, J.-F. and De Vries, J. E., IL-10 and viral IL-10 prevent IL-4-induced IgE synthesis by inhibiting the accessory cell function of monocytes. J. Immunol. 1993. 151: 12801289.
  • 29
    King, C. L., Gallin, J. I., Malech, H. L., Abramson, S. L. and Nutman, T. B., Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma. Proc. Natl. Acad. Sci. USA 1989. 86: 1008510089.
  • 30
    Schleimer, R. P., Sterbinsky, S. A., Kaiser, J., Bickel, C. A., Klunk, D. A., Tomioka, K., Newman, W., Luscinskas, F. W., Gimbrone, M. A., Jr., McIntyre, B. W. and Bochner, B. S., IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium: association with expression of VCAM-1. J. Immunol. 1992. 148: 10861092.
  • 31
    Akdis, M., Simon, H.-U., Weigl, L., Kreyden, O., Blaser, K. and Akdis, C. A., Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis. J. Immunol. 1999. 163: 466475.
  • 32
    Zuany-Amorim, C., Creminon, C., Nevers, M. C., Nahori, M.-A., Vergaftig, B. B. and Pretolani, M., Modulation by IL-10 of antigen-induced IL-5 generation, and CD4+ T lymphocyte and eosinophil infiltration into the mouse peritoneal cavity. J. Immunol. 1996. 157: 377384.
  • 33
    Hoffmann, K. F., Cheever, A. W. and Wynn, T. A., IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J. Immunol. 2000. 164: 64066416.
  • 34
    Bryan, S. A., O'Connor, B. J., Matti, S., Leckie, M. J., Kanabar, V., Khan, J., Warrington, S. J., Renzetti, L., Rames, A., Bock, J. A., Boyce, M. J., Hansel, T. T., Holgate, S. T. and Barnes, P. J., Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000. 356: 21492153.
  • 35
    Broide, D., Schwarze, J., Tighe, H., Gifford, T., Nguyen, M. D., Malek, S., Van Uden, J., Martin-Orozco, E., Gelfand, E. W. and Raz, E., Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness. J. Immunol. 1998. 161: 70547062.
  • 36
    Santeliz, J. V., Van Nest, G., Traquina, P., Larsen, E. and Wills-Karp, M., Amb a 1-linked CpG oligonucleotides reverse established airway hyperresponsiveness in a murine model of asthma. J. Allergy Clin. Immunol. 2002. 109: 455462.
  • 37
    Kritzik, S. R., Sieling, P. A. and Modlin, R. L., The role of Toll-like receptors in host defense against microbial infection. Curr. Opin. Immunol. 2001. 13: 104108.
  • 38
    Dong, Z., Qi, X. and Fidler, I. J., Tyrosine phosphorylation of mitogen-activated protein kinases is necessary for activation of murine macrophages by natural and synthetic bacterial products. J. Exp. Med. 1993. 177: 10711077.
  • 39
    Muller, M. A., Pfannes, S. D., Ayoub, M., Hoffmann, P., Bessler, W. G. and Mittenbuhler, K., Immunostimulation by the synthetic lipopeptide P3CSK4: TLR4-independent activation of the ERK1/2 signal transductionpathway in macrophages. Immunology. 2001. 103: 4960.
  • 40
    Akira, S., Takeda, K. and Kaisho, T., Toll-like receptors: critical proteins linking innate andacquired immunity. Nat. Immunol. 2001. 2: 675680.
  • 41
    Shirakawa, T., Enomoto, T., Shimazu, S.-I. and Hopkin, J. M., The inverse association between tuberculin responses and atopic disorder. Science 1997. 275: 7779.
  • 42
    Braun-Fahrländer, C., Gassner, M., Grize, L., Neu, U., Sennhauser, F. H., Varonier, H. S., Vuille, J. C. and Wüthrich, B., Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. Clin. Exp. Allergy 1999. 29: 2834.
  • 43
    Cookson, W. O. C. M. and Moffatt, M. F., Asthma: an epidemic in the absence of infection? Science. 1997. 275: 4142.
  • 44
    Baschang, G., Muramylpeptides and lipopeptides: studies towards immunostimulants. Tetrahedron 1989. 45: 63316360.
  • 45
    Alkan, S. S., Antigen-induced proliferation assay for mouse T lymphocytes. Response to a monovalent antigen. Eur. J. Immunol. 1978. 8: 112118.
  • 46
    Coyle, A. J., Tsuyuki, S., Bertrand, C., Huang, S., Aguet, M., Alkan, S. S. and Anderson, G. P., Mice lacking the IFN-gamma receptor have impaired ability to resolve a lung eosinophilic inflammatory response associated with a prolonged capacity of T cells to exhibit a Th2 cytokine profile. J. Immunol. 1996. 156: 26802685.
  • 47
    Alkan, S. S., Akdis, C. A. and Towbin, H., Chemiluminescent and enzyme-linked immuno assays forsensitive detection of human IFN-γ. J. Immunoassay 1994. 15: 217238.
  • 48
    De Waal Malefyt, R., Figdor, C. G., Huijbens, R., Mohan Peterson, S., Bennett, B., Culpepper, J., Dang, W., Zurawski, G. and De Vries, J. E., Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J. Immunol. 1993. 151: 63706381.
  • 49
    Sambrook, J., Hanahan, D., Rodgers, L. and Gething, M. J., Expression of human tissue-type plasminogen activator from lytic viral vectors and in established cell lines. Mol. Biol. Med. 1986. 3: 459481.
  • 50
    Kolbe, L., Heusser, C. H. and Kälsch, E., Isotype-associated recognition of allergen epitopes and its modulation by antigen dose. Immunology 1995. 84: 285289.