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Departments of
*
Pathology and of
Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106
Traditionally, protein Ags have been injected in CFA (oil with inactivated mycobacteria) to induce immunity and with IFA (oil alone) to induce tolerance. We report here that injection of hen eggwhite lysozyme, a prototypic Ag, in CFA-induced and IFA-induced pools of hen eggwhite lysozyme-specific memory T cells of comparable fine specificity, clonal size, and avidity spectrum, but with type-1 and type-2 cytokine signatures, respectively. This adjuvant-guided induction of virtually unipolar type-1 and type-2 immunity was observed with seven protein Ags and in a total of six mouse strains. Highly polarized type-1 and type-2 immunity are thus readily achievable through the choice of adjuvant, irrespective of the genetic bias of the host and of the nature of the protein Ag. This finding should have far-reaching implications for the development of vaccines against infectious and autoimmune diseases. Furthermore, our demonstration that Ag injected with IFA is as strongly immunogenic for T cells as it is with CFA shows that the presence of the mycobacteria determines not the priming of naive T cells through the second-signal link but the path of downstream differentiation toward CD4 memory cells that express either type-1 or type-2 cytokines.
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S. Saarelainen, T. Zeiler, J. Rautiainen, A. Narvanen, M. Rytkonen-Nissinen, R. Mantyjarvi, P. Vilja, and T. Virtanen Lipocalin allergen Bos d 2 is a weak immunogen Int. Immunol., April 1, 2002; 14(4): 401 - 409. [Abstract] [Full Text] [PDF]
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A. Y. Karulin, M. D. Hesse, H. C. Yip, and P. V. Lehmann Indirect IL-4 Pathway in Type 1 Immunity J. Immunol., January 15, 2002; 168(2): 545 - 553. [Abstract] [Full Text] [PDF]
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B. M. Naiman, D. Alt, C. A. Bolin, R. Zuerner, and C. L. Baldwin Protective Killed Leptospira borgpetersenii Vaccine Induces Potent Th1 Immunity Comprising Responses by CD4 and gamma delta T Lymphocytes Infect. Immun., December 1, 2001; 69(12): 7550 - 7558. [Abstract] [Full Text] [PDF]
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A. Billiau and P. Matthys Modes of action of Freund's adjuvants in experimental models of autoimmune diseases J. Leukoc. Biol., December 1, 2001; 70(6): 849 - 860. [Abstract] [Full Text] [PDF]
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 S. Mirshahidi, C.-T. Huang, and S. Sadegh-Nasseri Anergy in Peripheral Memory CD4+ T Cells Induced by Low Avidity Engagement of T Cell Receptor J. Exp. Med., September 10, 2001; 194(6): 719 - 732. [Abstract] [Full Text] [PDF]
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M. D. Hesse, A. Y. Karulin, B. O. Boehm, P. V. Lehmann, and M. Tary-Lehmann A T Cell Clone's Avidity Is a Function of Its Activation State J. Immunol., August 1, 2001; 167(3): 1353 - 1361. [Abstract] [Full Text] [PDF]
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J. D. Ahlers, I. M. Belyakov, S. Matsui, and J. A. Berzofsky Mechanisms of cytokine synergy essential for vaccine protection against viral challenge Int. Immunol., July 1, 2001; 13(7): 897 - 908. [Abstract] [Full Text] [PDF]
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K. G. Tournoy, J. C. Kips, and R. A. Pauwels The Allergen-Induced Airway Hyperresponsiveness in a Human-Mouse Chimera Model of Asthma Is T Cell and IL-4 and IL-5 Dependent J. Immunol., June 1, 2001; 166(11): 6982 - 6991. [Abstract] [Full Text] [PDF]
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O. S. Targoni, J. Baus, H. H. Hofstetter, M. D. Hesse, A. Y. Karulin, B. O. Boehm, T. G. Forsthuber, and P. V. Lehmann Frequencies of Neuroantigen-Specific T Cells in the Central Nervous System Versus the Immune Periphery During the Course of Experimental Allergic Encephalomyelitis J. Immunol., April 1, 2001; 166(7): 4757 - 4764. [Abstract] [Full Text] [PDF]
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H. Jyonouchi, S. Sun, T. Winship, and M. J. Kuchan Dietary Ribonucleotides Modulate Type 1 and Type 2 T-Helper Cell Responses against Ovalbumin in Young BALB/cJ Mice J. Nutr., April 1, 2001; 131(4): 1165 - 1170. [Abstract] [Full Text]
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D. Abraham, O. Leon, S. Leon, and S. Lustigman Development of a Recombinant Antigen Vaccine against Infection with the Filarial Worm Onchocerca volvulus Infect. Immun., January 1, 2001; 69(1): 262 - 270. [Abstract] [Full Text] [PDF]
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P. Matthys, K. Vermeire, H. Heremans, and A. Billiau The protective effect of IFN-{gamma} in experimental autoimmune diseases: a central role of mycobacterial adjuvant-induced myelopoiesis J. Leukoc. Biol., October 1, 2000; 68(4): 447 - 454. [Abstract] [Full Text]
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G. B. Lipford, T. Sparwasser, S. Zimmermann, K. Heeg, and H. Wagner CpG-DNA-Mediated Transient Lymphadenopathy Is Associated with a State of Th1 Predisposition to Antigen-Driven Responses J. Immunol., August 1, 2000; 165(3): 1228 - 1235. [Abstract] [Full Text] [PDF]
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B. M. Segal, J. T. Chang, and E. M. Shevach CpG Oligonucleotides Are Potent Adjuvants for the Activation of Autoreactive Encephalitogenic T Cells In Vivo J. Immunol., June 1, 2000; 164(11): 5683 - 5688. [Abstract] [Full Text] [PDF]
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P. S. Heeger, T. Forsthuber, C. Shive, E. Biekert, C. Genain, H. H. Hofstetter, A. Karulin, and P. V. Lehmann Revisiting Tolerance Induced by Autoantigen in Incomplete Freund's Adjuvant J. Immunol., June 1, 2000; 164(11): 5771 - 5781. [Abstract] [Full Text] [PDF]
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G. Foucras, L. Gapin, C. Coureau, J. M. Kanellopoulos, and J.-C. Guery Interleukin 4-producing CD4 T Cells Arise from Different Precursors Depending on the Conditions of Antigen Exposure In Vivo J. Exp. Med., February 21, 2000; 191(4): 683 - 694. [Abstract] [Full Text] [PDF]
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A. Y. Karulin, M. D. Hesse, M. Tary-Lehmann, and P. V. Lehmann Single-Cytokine-Producing CD4 Memory Cells Predominate in Type 1 and Type 2 Immunity J. Immunol., February 15, 2000; 164(4): 1862 - 1872. [Abstract] [Full Text] [PDF]
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D. C. Lenz, N. A. Wolf, and R. H. Swanborg Strain Variation in Autoimmunity: Attempted Tolerization of DA Rats Results in the Induction of Experimental Autoimmune Encephalomyelitis J. Immunol., August 15, 1999; 163(4): 1763 - 1768. [Abstract] [Full Text] [PDF]
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