Mechanisms of immunotherapy

• Published in: Journal of allergy and clinical immunology 2004-06, Vol.113 (6), p.1025-1034
• Main Authors: Till, Stephen J., Francis, James N., Nouri-Aria, Kayhan, Durham, Stephen R.
• Format: Article
• Language: English
• Subjects: Airway management; Allergies; allergy; Animals; Biological and medical sciences; Desensitization, Immunologic; Disease; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hay fever; Humans; IgE; IL-10; Immune system; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunoglobulin G - classification; Immunopathology; Immunotherapy; Interleukin-10 - biosynthesis; Lymphocytes; Medical sciences; regulatory T cells; T cell receptors; T-Lymphocytes - immunology; Venom
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.03.024

Specific allergen injection immunotherapy is highly effective in IgE-mediated diseases, such as allergic rhinitis and venom anaphylaxis. Immunotherapy inhibits both early and late responses to allergen exposure. Immunotherapy is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Immunotherapy acts on T cells to modify peripheral and mucosal T H2 responses to allergen in favor of T H1 responses. Recent studies have identified increased IL-10 production in peripheral blood and mucosal surfaces after immunotherapy. IL-10 has numerous potential antiallergic properties, including suppression of mast cell, eosinophil, and T-cell responses, as well as acting on B cells to favor heavy chain class switching to IgG4. These IL-10–producing cells might be so-called regulatory T cells and appear to be identified by the CD4 +CD25 + phenotype. Studies in mice suggest that dendritic cells play a vital role in induction of regulatory T cells. Novel approaches to immunotherapy currently being explored include the use of adjuvants, such as monophosphoryl lipid A or nucleotide immunostimulatory sequences derived from bacteria that potentiate T H1 responses. Alternative strategies include the use of allergen-derived peptides or modified recombinant allergen vaccines that act on T cells while minimizing the IgE-dependent mast cell activation that is dependent on the native allergen conformation.