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Genes of tolerance.

C A Akdis1, K Blaser, M Akdis

  • 1Swiss Institute of Allergy and Asthma Research, Davos, Switzerland.

Allergy
|August 5, 2004
PubMed
Summary

T-regulatory cells (T(Reg)) are crucial for peripheral tolerance to allergens by suppressing immune responses. They modulate T-cell proliferation and cytokine secretion, offering potential for novel allergy therapies.

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Area of Science:

  • Immunology
  • Allergy Research
  • Cellular Biology

Background:

  • Peripheral T-cell tolerance is maintained by mechanisms including activation-induced cell death, anergy, and T-regulatory cell (T(Reg)) mediated immune modulation.
  • Anergy, tolerance, and active suppression are increasingly viewed as interconnected processes involving shared cellular mechanisms.
  • Skewing allergen-specific effector T cells towards T(Reg) cells is vital for healthy immune responses to allergens and successful immunotherapy.

Purpose of the Study:

  • To explore the multifaceted roles of T-regulatory cells in peripheral tolerance to allergens.
  • To elucidate the mechanisms by which T(Reg) cells suppress allergic inflammation and modulate immune responses.
  • To highlight the potential of T(Reg) cell-mediated tolerance in developing novel therapeutic strategies for allergic diseases.

Main Methods:

  • Review of existing evidence on T-regulatory cell function in allergen tolerance.
  • Analysis of T(Reg) cell-associated changes in T-cell proliferation and cytokine profiles (Th1, Th2).
  • Investigation of the impact of mediators like histamine receptor 2 on peripheral tolerance.

Main Results:

  • T(Reg) cell activity is characterized by suppressed allergen-specific T-cell proliferation and reduced Th1/Th2 cytokine secretion.
  • Increased interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) from T(Reg) cells inhibit immunoglobulin E (IgE) production and promote IgG4/IgA.
  • T(Reg) cells suppress key effector cells in allergic inflammation, including mast cells, basophils, and eosinophils.

Conclusions:

  • Peripheral tolerance to allergens is orchestrated by multiple active suppression mechanisms.
  • T(Reg) cells play a central role by regulating antibody isotypes and effector cells towards a healthy immune profile.
  • These findings open avenues for novel therapeutic interventions targeting allergic diseases through T(Reg) cell modulation.

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