Springer Seminars in Immunopathology

, Volume 25, Issue 3–4, pp 271–279

Mechanisms of tolerance to inhalant allergens: the relevance of a modified Th2 response to allergens from domestic animals

  • Thomas A. E. Platts-Mills
  • Judith A. Woodfolk
  • Elizabeth A. Erwin
  • Rob Aalberse
Original Paper


Subjects can be “non-allergic” because (1) they are not exposed, (2) they fail to make an immune response, or (3) they make an immune response that does not include IgE antibodies (Ab). The recent observation that children raised in a house with a cat are less likely to become allergic to cat allergen than those who only get indirect exposure provides a model to investigate the factors controlling allergic responses. Many of these highly exposed children have made an IgG and IgG4 Ab response to Fel d 1 without IgE Ab, i.e., a “modified Th2 response”. In countries where cats are a major cause of asthma, the presence of a cat may decrease the risk of asthma. By contrast, in countries with high exposure to dust mites, cats can induce specific tolerance to Fel d 1 without influencing asthma or the IgE Ab response to dust mites. Using overlapping peptides to investigate T cell responses to Fel d 1 suggests that the structure of the molecule plays a special role in inducing the T cell responses that can “control” the immune response to cat allergens. This T cell response is characterized by high levels of IL-10 production, but this is not restricted to those who have made a modified Th2 response. The results suggest that there are major differences in the immune response to different allergens that profoundly affect their role in allergic disease. Dust mite and cockroach differ from cat (and rat) allergens not only in the quantity inhaled and the particles’ sizes but also in the biochemistry of the molecule.


Tolerance Inhalant allergen Modified Th2 response Domestic animals 


  1. 1.
    Aalberse RC, Gaag R van der, Leeuwen J van (1983) Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response. J Immunol 130:722Google Scholar
  2. 2.
    Akdis CA, Blesken T, Akdis M, et al (1998) Role of interleukin-10 in specific immunotherapy. J Clin Invest 102:98Google Scholar
  3. 3.
    Busse WW, Lemanske RF (2001) Asthma. N Engl J Med 344:350Google Scholar
  4. 4.
    Creticos PS, Norman PS (1987) Immunotherapy with allergens. JAMA 258:2874Google Scholar
  5. 5.
    Custis NJ, Woodfolk JA, Vaughan JW, et al (2003) Quantitative measurements of airborne allergens from dust mites, dogs, and cats using an ion charging device. Clin Exp Allergy (in press)Google Scholar
  6. 6.
    Custovic A, Hallam CL, Simpson BM, et al (2001) Decreased prevalence of sensitization to cats with high exposure to cat allergen. J Allergy Clin Immunol 108:537Google Scholar
  7. 7.
    Eggleston PA, Rosenstreich D, Lynn H, et al (1998) Relationship of indoor allergen exposure to skin test sensitivity in inner-city children with asthma. J Allergy Clin Immunol 102:563Google Scholar
  8. 8.
    Eisenbarth SC, Piggott DA, Huleatt JW, et al (2002) Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med 196:1645Google Scholar
  9. 9.
    Gelber LE, Seltzer LH, Bouzoukis JK, et al (1993) Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital. Am Rev Respir Dis 147:573Google Scholar
  10. 10.
    Gleich GJ, Zimmermann EM, Henderson LL, et al (1982) Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study. J Allergy Clin Imunol 70:261Google Scholar
  11. 11.
    Hesselmar B, Aberg N, Eriksson B, et al (1999) Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy 29:611Google Scholar
  12. 12.
    Jeannin P, Lecoanet S, Delneste Y, et al (1998) IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 160:3555Google Scholar
  13. 13.
    Lau S, Illi S, Sommerfeld C (2000) Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Lancet 356:1392Google Scholar
  14. 14.
    Luczynska CM, Arruda LK, Platts-Mills TAE, et al (1989) A two-site monoclonal antibody ELISA for the quantification of the major Dermatophagoides spp. allergens, Der p I and Der f I. J Immunol Methods 118:227Google Scholar
  15. 15.
    Marsh DG (1976) Atopic allergy; a model for studying the genetics of immune response in man. Birth Defects Orig Artic Ser 12:223Google Scholar
  16. 16.
    Oldfield WL, Larche M, Kay AAB (2002) Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomized controlled trial. Lancet 360:47Google Scholar
  17. 17.
    Ownby DR, Johnson CC, Peterson EL (2002) Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 288:963Google Scholar
  18. 18.
    Peat JK, Tovey E, Toelle BG, et al (1996) House dust mite allergens. A major risk factor for childhood asthma in Australia. Am J Respir Crit Care Med 153:141Google Scholar
  19. 19.
    Perzanowski MS, Ronmark E, Platts-Mills TAE, et al (2002) Effect of cat and dog ownership on sensitization and development of asthma among preteenage children. Am J Respir Crit Car Med 166:696Google Scholar
  20. 20.
    Platts-Mills TAE (1979) Local production of IgG, IgA and IgE antibodies in grass pollen hay fever. J Immunol 122:2218Google Scholar
  21. 21.
    Platts-Mills TAE (1982) Type I or immediate hypersensitivity. Hay fever and asthma. In: Lachmann PJ, Peters DK (eds) Clinical aspects of Immunology, vol 1. Blackwell, Oxford, p 579Google Scholar
  22. 22.
    Platts-Mills TAE, Vervloet D, Thomas WR, et al (1997) Indoor allergens and asthma: report of the Third International Workshop. J Allergy Clin Immunol 100:S2Google Scholar
  23. 23.
    Platts-Mills TAE, Vaughan JV, Squillace S, et al (2001) Sensitization, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 357:752Google Scholar
  24. 24.
    Platts-Mills TAE, Perzanowski M, Woodfolk JA, et al (2002) Relevance of early or current pet ownership to the prevalence of allergic disease. Clin Exp Allergy 32:335Google Scholar
  25. 25.
    Platts-Mills TAE, Erwin EA, Allison AB, et al (2003) The relevance of maternal immune responses to inhalant allergens to maternal symptoms, passive transfer to the infant, and development of antibodies in the first two years of life. J Allergy Clin Immunol 111:123Google Scholar
  26. 26.
    Prescott SL, Macaubas C, Smallacombe T, et al (1999) Development of allergen-specific T-cell memory in atopic and normal children. Lancet 353:196Google Scholar
  27. 27.
    Romagnani S (2001) T-cell responses in allergy and asthma. Curr Opin Allergy Clin Immunol 1:73Google Scholar
  28. 28.
    Ronmark E, Jonsson E, Platts-Mills TAE, et al (2001) Incidence and remission of asthma in schoolchildren: report from the obstructive lung disease in northern Sweden studies. Pediatrics 107:E37Google Scholar
  29. 29.
    Rowntree S, Platts-Mills TAE, Cogswell JJ, et al (1987) A subclass IgG4-specific antigen-binding radioimmunoassay (RIA): comparison between IgG and IgG4 antibodies to food and inhaled antigens in adult atopic dermatitis after desensitization treatment and during development of antibody responses in children. J Allergy Clin Immunol 80:622Google Scholar
  30. 30.
    Schulz O, Sewell HF, Shakib F (1998) Proteolytic cleavage of CD25, the α subunit of the human T cell Interleukin 2 receptor, by Der p 1, a major mite allergen with cysteine protease activity. J Exp Med 187:271Google Scholar
  31. 31.
    Sears MR, Hervison GP, Holdaway MD, et al (1989) The relative risks of sensitivity to grass pollen, house dust mite, and cat dander in the development of childhood asthma. Clin Exp Allergy 19:419Google Scholar
  32. 32.
    Sporik R, Holgate ST, Platts-Mills TAE, et al (1990) Exposure to house-dust mite allergen (Der p 1) and the development of asthma in childhood. N Engl J Med 323:502Google Scholar
  33. 33.
    Sporik R, Squillace SP, Ingram JM, et al (1999) Mite, cat, and cockroach exposure, allergen sensitization and asthma in children. A case-control study of three schools. Thorax 54:675Google Scholar
  34. 34.
    Wan H, Winton HL, Soeller C, et al (1999) Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest 104:3Google Scholar
  35. 35.
    Wang SZ, Rosenberger CL, Espindola TM, et al (2001) CCSP modulates airway dysfunction and host responses in a Ova-challenged mouse model. Am J Physiol Lung Cell Mol Physiol 281:L1303Google Scholar
  36. 36.
    Wide L, Benich H, Johansson SG (1967) Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet II:1105Google Scholar
  37. 37.
    Wierenga EA, Snoek M, Jansen HM, et al (1991) Human atopen-specific types 1 and 2 T helper cell clones. J Immunol 147:2942Google Scholar
  38. 38.
    Woodfolk JA, Platts-Mills TAE (2001) Diversity of the human allergen-specific T cell repertoire associated with distinct skin test reactions: delayed-type hypersensitivity-associated major epitopes induce Th1- and Th2-dominated responses. J Immunol 167:5412Google Scholar
  39. 39.
    Woodfolk JA, Platts-Mills TAE (2002) The immune response to intrinsic and extrinsic allergens. Determinants of allergic disease. Int Arch Allergy Immunol 129:277Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Thomas A. E. Platts-Mills
    • 1
  • Judith A. Woodfolk
    • 1
  • Elizabeth A. Erwin
    • 1
  • Rob Aalberse
    • 1
  1. 1.Asthma and Allergic Disease Center, University of VirginiaUniversity Health SystemsCharlottesvilleUSA

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