Allergy immunotherapy and inhibition of Th2 immune responses: a sufficient strategy?
Th2 immune responses mediated by the secretion of IL-4, IL-5 and IL-13 are key in the pathogenesis of atopic disorders, including allergen-induced asthma, rhinoconjunctivitis and anaphylaxis. Although such responses are downregulated to some degree by conventional specific immunotherapy, this approach is only partially effective and has a substantial risk of adverse effects. Many strategies for immunotherapeutic prophylaxis and for treatment of atopic diseases have been devised on the basis of mouse allergy and autoimmune models, including the downregulation of Th2 responses by the induction of regulatory T cell activity, Th2 to Th1 immune deviation, Th1 crossregulation of Th2 immune responses, anergy and immunosuppressive cytokines. The blockade of events that are not allergen-specific, such as T cell costimulation and downstream events dependent on IgE, cytokines and chemokines, has also been pursued. With the exception of monoclonal antibody therapy for the blockade of IgE effector function, the application of most of these strategies to humans is at an early stage. Whether the inhibition of Th2 responses without concurrent downregulation of Th1 responses will be sufficient for allergic immunotherapy, particularly for atopic dermatitis and asthma, is an important but unresolved issue.
Lewis
David B
DB
Division of Immunology and Transplantation Biology, Department of Pediatrics, CCSR Building, Room 2115b, 269 Campus Drive, Stanford University School of Medicine, Stanford, California 94305-5164, USA. dblewis@stanford.edu
D000818:Animals; D018925:Chemokines / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology
C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007073:Immunoglobulin E