Allergy in the 21st Century: New Answers to Old Questions
23rd Symposium of the Collegium Internationale Allergologicum
May 18-23, 2000, Hakone, Japan
Editors: Takeru Ishikawa, Kumamoto; Terumasa Miyamoto, Tokyo; Hirokazu Okudaira, Tokyo; Hisao Tomioka, Chiba; Rudolf Valenta, Vienna; Dietrich Kraft, Vienna

Regulatory Pathways

Mechanism of IL-10-Induced T Cell Inactivation in Allergic Inflammation and Normal Response to Allergens
Cezmi A. Akdis, Andrea Joss, Mübeccel Akdis, Kurt Blaser

Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland

Address of Corresponding Author

Int Arch Allergy Immunol 2001;124:180-182 (DOI: 10.1159/000053704)

  Key Words

• T cell
• Interleukin 10
• Tolerance
• Anergy
• Immunotherapy, specific

  Abstract

Background: Induction of specific unresponsiveness (tolerance/anergy) in peripheral T cells and recovery by cytokines from the tissue microenvironment represent two key steps in specific immunotherapy (SIT) with whole allergen or antigenic T cell peptides. Methods: Antigen-specific T cell responses and molecular mechanisms of T cell inactivation were investigated during conventional SIT, T cell epitope peptide immunotherapy and natural exposure to bee venom in allergic and hyperimmune individuals. Results: T cell unresponsiveness, initiated by autocrine action of IL-10, is characterized by suppressed proliferative and cytokine responses. The unresponsive T cells can be reactivated by different cytokines that may mimic the microenvironmental cytokine influence. IL-10 initiates peripheral tolerance by blocking the CD28 costimulatory signal in T cells. Coprecipitation experiments reveal that upon stimulation CD28 and IL-10 receptor are physically associated in T cells. Accordingly, IL-10 binding to its receptor inhibits CD28 tyrosine phosphorylation, the initial step of the CD28 signaling pathway. This leads to inhibition of phosphatidylinositol 3-kinase p85 binding to CD28. IL-10 only affects T cells that receive a stimulation with low numbers of triggered T cell receptors and that require costimulatory signals by CD28. Conclusion: These data demonstrate the pivotal role of autocrine IL-10 and the interaction of its receptor with CD28 in the induction of T cell tolerance as an immunoregulatory mechanism controlling antigen-specific T cell responses.

Copyright © 2001 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. Cezmi A. Akdis
Swiss Institute of Allergy and Asthma Research (SIAF)
Obere Strasse 22
CH-7270 Davos (Switzerland)
Tel. +41 81 410 08 48, Fax +41 81 410 08 40, E-Mail akdism@siaf.unizh.ch

  Article Information

Number of Print Pages : 3
Number of Figures : 0, Number of Tables : 0, Number of References : 14