Healthy immune response to allergens - Frequency and phenotype of allergen-specific T-cells define mechanisms of peripheral tolerance


Akdis M., Manhart C., Karamloo F., Marcovic-Housley Z., Vrtala S., Valenta R., ...More

27th Symposium of the Collegium-Internationale-Allergologicum, Southampton, England, 01 November 2002, pp.76-78 identifier

  • Publication Type: Conference Paper / Full Text
  • City: Southampton
  • Country: England
  • Page Numbers: pp.76-78
  • Keywords: T-cell, tolerance, allergy, interleukins, interferons, IN-VITRO, DIFFERENTIAL REGULATION, IMMUNOTHERAPY, IGE, ANTIBODIES, INDUCTION, IL-10
  • Istanbul University Affiliated: No

Abstract

The characterization of normal immune response to environmental allergens/antigens in healthy individuals may enlighten the pathogenesis of a diseased immune response in allergic patients. We investigated the allergen-specific T-cell profiles of healthy individuals against environmental antigens/allergens (rPyr c 5 from pear, rCor a from hazelnut, rBet v 1 and rBet v 6 from birch pollen, rDer p 1 from house dust mite, rPhl p 2 and rPhl p 5a from grass pollen) to which healthy individuals are exposed. Consistently, the allergen-specific IL-10- andTGF-beta-producing T-cells represented the dominant T-cell subset against environmental allergens in healthy individuals. These cells were in the CD4(+) CD25(+) CD45RO(+)T-cell subset and expressed high levels of IL-10 receptor, TGF-beta receptor I and II, as well as CTLA-4. Depletion of this particular subset or blocking of IL-10 and TGF-beta significantly enhanced the allergen-specific T-cell proliferation and production of IL-13 and IFN-gamma, demonstrating the role of these cells in allergen-specific peripheral T-cell tolerance. Similarly, healthy beekeepers who had recently been stung by high numbers of bees (more than 20 stings) represent naturally tolerant individuals and showed increased numbers of IL-10-producing CD4(+) CD25(+) CD4SRO(+) T-cells. Seven days after multiple bee stings, a significant increase in the frequency of bee venom major allergen phospholipase A(2)-specific IL-10-producing T-cells and a decrease in JL-4- and IFN-gamma-producing T-cells was observed. Together these results demonstrate that healthy immune response to allergens is maintained by a shift to a regulatory/suppressor T-cell phenotype and the cooperation of multiple suppressor mechanisms.