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*
Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University, Stanford, CA 94305; and
Respiratory Medicine Unit, University of Edinburgh Medical School, Edinburgh, United Kingdom
In this study we examined the immunological parameters underlying the natural immunity to inhaled nonpathogenic proteins. We addressed this question by examining the effect of intranasal exposure to OVA in both wild-type mice and mice reconstituted with OVA-TCR transgenic CD4+ T cells. Intranasal administration of OVA induced an initial phase of activation during which CD4+ T cells were capable of proliferating and producing cytokines. Although many of the OVA-specific CD4+ T cells were subsequently depleted from the lymphoid organs, a stable population of such T cells survived but remained refractory to antigenic rechallenge. The unresponsive state was not associated with immune deviation due to selective secretion of Th1- or Th2-type cytokines, and the presence of regulatory CD8+ T cells was not required. Moreover, neutralization of the immunosuppressive cytokines IL-10 and TGF-ß did not abrogate the induction of tolerance. Inhibition of the interaction of T cells with CD86, but not CD80, at the time of exposure to intranasal Ag prevented the development of unresponsiveness, while selective blockade of CTLA-4 had no effect. Our results suggest that intranasal exposure to Ags results in immunological tolerance mediated by functionally impaired CD4+ T cells via a costimulatory pathway that requires CD86.
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J.-i. Masuyama, S. Kaga, S. Kano, and S. Minota A Novel Costimulation Pathway Via the 4C8 Antigen for the Induction of CD4+ Regulatory T Cells J. Immunol., October 1, 2002; 169(7): 3710 - 3716. [Abstract] [Full Text] [PDF]
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K. A. Frauwirth, M.-L. Alegre, and C. B. Thompson CTLA-4 Is Not Required for Induction of CD8+ T Cell Anergy In Vivo J. Immunol., November 1, 2001; 167(9): 4936 - 4941. [Abstract] [Full Text] [PDF]
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A. G. Jarnicki, T. Tsuji, and W. R. Thomas Inhibition of mucosal and systemic Th2-type immune responses by intranasal peptides containing a dominant T cell epitope of the allergen Der p 1 Int. Immunol., October 1, 2001; 13(10): 1223 - 1231. [Abstract] [Full Text] [PDF]
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 A. D Dick, V. Sharma, and J. Liversidge Single dose intranasal administration of retinal autoantigen generates a rapid accumulation and cell activation in draining lymph node and spleen: implications for tolerance therapy Br J Ophthalmol, August 1, 2001; 85(8): 1001 - 1006. [Abstract] [Full Text] [PDF]
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H.-R. Jiang, N. Taylor, L. Duncan, A. D Dick, and J. V Forrester Total dose and frequency of administration critically affect success of nasal mucosal tolerance induction Br J Ophthalmol, June 1, 2001; 85(6): 739 - 744. [Abstract] [Full Text] [PDF]
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D. M. Walter, C. P. Wong, R. H. DeKruyff, G. J. Berry, S. Levy, and D. T. Umetsu IL-18 Gene Transfer by Adenovirus Prevents the Development of and Reverses Established Allergen-Induced Airway Hyperreactivity J. Immunol., May 15, 2001; 166(10): 6392 - 6398. [Abstract] [Full Text] [PDF]
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 L. Cohn Food for Thought . Can Immunological Tolerance Be Induced to Treat Asthma? Am. J. Respir. Cell Mol. Biol., May 1, 2001; 24(5): 509 - 512. [Full Text]
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 A. Hänninen, A. Braakhuis, W. R. Heath, and L. C. Harrison Mucosal Antigen Primes Diabetogenic Cytotoxic T-Lymphocytes Regardless of Dose or Delivery Route Diabetes, April 1, 2001; 50(4): 771 - 775. [Abstract] [Full Text]
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E. Prager, G. Staffler, O. Majdic, M. D. Saemann, S. Godar, G. J. Zlabinger, and H. Stockinger Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells J. Immunol., February 15, 2001; 166(4): 2364 - 2371. [Abstract] [Full Text] [PDF]
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K. Dabbagh, Y. Xiao, C. Smith, P. Stepick-Biek, S. G. Kim, W. J. E. Lamm, D. H. Liggitt, and D. B. Lewis Local Blockade of Allergic Airway Hyperreactivity and Inflammation by the Poxvirus-Derived Pan-CC-Chemokine Inhibitor vCCI J. Immunol., September 15, 2000; 165(6): 3418 - 3422. [Abstract] [Full Text] [PDF]
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D. C. Tsitoura, S. Kim, K. Dabbagh, G. Berry, D. B. Lewis, and D. T. Umetsu Respiratory Infection with Influenza A Virus Interferes with the Induction of Tolerance to Aeroallergens J. Immunol., September 15, 2000; 165(6): 3484 - 3491. [Abstract] [Full Text] [PDF]
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M. Astori, C. von Garnier, A. Kettner, N. Dufour, G. Corradin, and F. Spertini Inducing Tolerance by Intranasal Administration of Long Peptides in Naive and Primed CBA/J Mice J. Immunol., September 15, 2000; 165(6): 3497 - 3505. [Abstract] [Full Text] [PDF]
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K. A. Frauwirth, M.-L. Alegre, and C. B. Thompson Induction of T Cell Anergy in the Absence of CTLA-4/B7 Interaction J. Immunol., March 15, 2000; 164(6): 2987 - 2993. [Abstract] [Full Text] [PDF]
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