Abstract
Oral tolerance is an important approach in allergic diseases and murine model can provide useful information to improve its understanding and therapeutic measures. To address the influence of non-related allergen sensitization in immunized mice with the mite Blomia tropicalis (Bt) or ovalbumin (OVA) or with both Bt/OVA allergens. Furthermore, we sought to verify oral tolerance effect in the Bt/OVA co-immunization model. Mice sensitized with Bt and then exposed to OVA developed an enhanced IgE response to both allergens; contrariwise, this effect was not observed when OVA-sensitization was prior to Bt-sensitization. Co-injection of Bt and OVA led to a dominant IgE response towards OVA over Bt, which was not observed when co-immunization was performed with a 240-fold less amount of OVA. Induction of oral tolerance with OVA, prior to co-immunization, suppressed IgE response to both allergens, probably as a consequence of the increased levels of IFN-γ found in these animals. The results evidenced that, depending on allergenic potential, new allergen exposure may exert an adjuvant effect to the first allergen used in the sensitization. The bystander suppression to non-related allergens through oral tolerance should be a useful mechanism to control sensitization to new allergens.
Similar content being viewed by others
References
Arlian LG, Vyszenski-Moher DL, Caldas FE: Allergenicity of the mite, Blomia tropicalis. J Allergy Clin Immunol 9:1042–1050, 1993
Arruda LK, Vailes LD, Platts-Mills TA, Fernandes-Caldas E, Montealegre F, Lin KL, Chua KY, Rizzo MC, Naspitz CK, Chapman MD: Sensitization to Blomia tropicalis in patients with asthma and identification of allergen Blot5. Am J Resp Crit Care Med 155:343–350, 1997
Sato MN, Oliveira CR, Futata EA, Victor JR, Maciel M, Fusaro AE, Carvalho AF, Duarte AJS: Oral tolerance induction to Dermathophagoides pteronyssinus and Blomia tropicalis in sensitized mice: Occurrence of natural autoantibodies to immunoglobulin E. Clin Exp Allergy 32:1667–1674, 2002
Carvalho AF, Fusaro AE, Oliveira CR, Brito CA, Duarte AJS, Sato MN: Blomia tropicalis and Dermatophagoides pteronyssinus mites evoke distinct patterns of airway cellular influx in type I hypersensitivity murine model. J Clin Immunol 24:533–541, 2004
Silvestri M, Rossi GA, Cozzani S, Pulvirenti G, Fasce L: Age-dependent tendency to become sensitized to other classes of aeroallergens in atopic asthmaric children. Ann Allergy Asthma Immunol 83:335–340, 1999
Purello-D’Ambrosio F, Gangemi S, Merendino RA, Isola S, Puccinelli P, Parmiani S, Ricciardi L: Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study. Clin Exp Allergy 31:1295–1302, 2001
TePas CE, Umetsu DT: Immunotherapy of asthma and allergic diseases. Curr Opin Pediatr 12:574–578, 2000
Mowat AM: Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 3:331–341, 2003
Strobel S, Mowat AM: Immune responses to dietary antigens: Oral tolerance. Immunol Today 19:173–181, 1998
Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL: Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor-β after antigen-specific triggering. Proc Natl Acad Sci USA 89:421–425, 1992
Chen Y, Kuchroo VK, Inobe JI, Hafler DA, Weiner HL: Regulatory T cell clones induced by oral tolerance: Suppression of autoimmune encephalomyelitis. Science 265:1237–1240, 1994
Weiner HL, Friedman A, Miller A, Khoury SJ, Al-Sabbagh A, Santos LMB, Sayegh M, Nussenblatt DE, Trentham DA, Hafler DA: Oral tolerance: Immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu Rev Immunol 12:809–837, 1994
Faria AM, Weiner HL: Oral tolerance mechanisms and therapeutic applications. Adv Immunol 73:153–264, 1999
van Halteren AG, van Der Cammem MJ, Cooper D, Savelkoul HF, Kraal G, Holt, PG: Regulation of antigen-specific IgE, IgG1 and mast cell responses to ingested allergen by mucosal tolerance induction. J Immunol 159:3009–3015, 1997
Holt PG, Batty JE, Turner KJ: Inhibition of specific IgE responses in mice by pre-exposure to inhaled antigen. Immunology 42:409–417, 1981
Sato MN, Carvalho AF, Silva AO, Junior MM, Fusaro AE, Duarte AJS: Low dose orally administered antigen down-regulates the T helper type 2-response in a murine model of dust mite hypersensitivity. Immunology 98:338–344, 1999
Melamed D, Fishman-Lovell J, Uni Z, Weiner HL, Friedman A: Peripheral tolerance of Th2 lymphocytes induced by continuos feeding of ovalbumin. Int Immunol 8:717–724, 1996
Friedman A, Weiner HL: Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proc Natl Acad Sci USA 91:6688–6692, 1994
Chen Y, Inobe I, Marks R, Gonella P, Kuchroo VK, Weiner HL: Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature 376:177–180, 1995
Strober W, Kelsall B, Fuss I, Marth T, Ludviksson B, Ehrhardt, R, Neurath M: Reciprocal IFN-gamma and TGF-beta responses regulate the occurrence of mucosal inflammation. Immunol Today 18:61–64, 1997
Briner TJ, Mei-Chang Kuo, Kathleen MK, Rogers BL, Greenstein JL: Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen fel d I. Immunology 90:7608–7612, 1993
Weiner HL: Oral tolerance: Immune mechanisms and the generation of Th3—type TGF-beta-secreting regulatory cells. Microbes Infect 3:947–954, 2001
Miller A, Lider O, Weiner HL: Antigen-driven bystander suppression after oral administration of antigens. J Exp Med 174:791–798, 1991
Mota I, Wong D: Homologous passive cutaneous anaphylaxis in the mouse. Life Sci 8:813–820, 1969
Thomas WR, Hales BJ, Smith W: Blomia tropicalis: More than just another source of mite allergens. Clin Exp Allergy 33:416–418, 2003
Holt PG, Prescott SL, Ng TW: Cellular immune responses to ovalbumin and house dust mite in egg-allergic children. Allergy 57:207–214, 2002
von Garnier C, Astori M, Kettner A, Dufour N, Corradin G, Spertini F: In vivo kinetics of the immunoglobulin E response to allergen: Bystander effect of coimmunization and relationship with anaphylaxis. Clin Exp Allergy 32:401–410, 2002
Friedman A: Induction of anergy in Th1 lymphocytes by oral tolerance. Ann NY Acad Sci 778:103–110, 1996
Marth T, Strober W, Kelsall BL: High dose oral tolerance in ovalbumin TCR-transgenic mice: Systemic neutralization of IL-12 augments TGF-β secretion and T cell apoptosis. J Immunol 157:2348–2357, 1996
Kelsall BL, Ehrhardt RO, Strober W: Induction of a primary IFN-γ response by Peyer’s patch dendritic cells is mediated by IL-12 and inhibited by IL-4. FASEB J 8:A207, 1994
Kweon MN, Fujihashi K, VanCott JL, Higuchi K, Yamamoto M, McGhee JR, Kiyono H: Lack of orally induced systemic unresponsiveness in IFN-γ Knockout mice. J Immunol 160:1687–1693, 1998
Finkelman FD, Lees A, Birnanbaum R, Gause WC, Morris SC: Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion. J Immunol 157:1406–1414, 1996
Viney JL, Mowat AM, O’Malley JM, Williamson E, Fanger NA: Expanding dendritic cells in vivo enhances the induction of oral tolerance. J Immunol 160:5815–5825, 1998
Lundin BS, Dahlgren UI, Hanson LA, Telemo E: Oral tolerization leads to active suppression and bystander tolerance in adult rats while anergy dominates in young rats. Scand J Immunol 43:56–63, 1996
Dahlman Hoglund A, Hanson LA, Ahlstedt S: Induction of oral tolerance with effects on numbers of IgE-carrying mast cells and on bystander suppression in young rats. Clin Exp Immunol 108:128–137, 1997
Karlsson MR, Kahu H, Hanson LA, Telemo E, Dahlgren UI: Tolerance and bystander suppression, with involvement of CD25-positive cells, is induced in rats receiving serum from ovalbumin-fed donors. Immunology 100:326–333, 2000
Chang XZ, Izikson L, Liu L, Weiner HL: Activation of CD25 + CD4 + Regulatory T cells by oral antigen administration. J Immunol 167:4245–4253, 2001
Koenen HJ, Fasse E, Joosten I: IL-15 and cognate antigen successfully expand de novo-induced human antigen-specific regulatory CD4(+) T cells that require antigen-specific activation for suppression. J Immunol 171:6431–6441, 2003
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Oliveira, C.R., Taniguchi, E.A.F., Fusaro, A.E. et al. Bystander Effect in Synergy to Anergy in Oral Tolerance of Blomia Tropicalis/Ovalbumin Murine Co-Immunization Model. J Clin Immunol 25, 153–161 (2005). https://doi.org/10.1007/s10875-005-2821-3
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10875-005-2821-3