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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2013007046
pages 389-414

Antigen-Specific Tolerance in Immunotherapy of Th2-Associated Allergic Diseases

Charles B. Smarr
Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611
Paul J. Bryce
Medicine and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611
Stephen D. Miller
Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611

ABSTRACT

Allergic diseases are an increasing health concern, particularly in the developed world. The standard clinical approach to treatment of allergic disease focuses on allergen avoidance and symptom control but does little to address the underlying Th2 bias of disease. Specific immunotherapy (SIT) consisting of controlled administration of allergen, however, has been demonstrated to successfully induce desensitization and tolerance in an antigen-specific manner for a variety of Th2-mediated diseases. This review focuses on the mechanisms by which current SIT approaches induce tolerance as well as discussing attempts to modify the safety and efficacy of SIT. These refinements focus on three major aspects of SIT: the route of antigen administration, modification of the antigen to remove allergenic epitopes and reduce adverse events and choice of adjuvant used to induce tolerance and/or immune deviation from Th2 to Th1 and regulatory T-cell (Treg) phenotypes. Synthesis of these recent developments in SIT provides considerable promise for more robust therapies with improved safety profiles to improve resolution of allergic disease and its associated costs.


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