Control and regulation of peripheral tolerance in allergic inflammatory disease: therapeutic consequences.
During the past few years there has been significant pro - gress in understanding the mechanisms by which abnormal T-cell responses are generated in allergic diseases. Peripheral T-cell tolerance to environmental antigens is crucial for a healthy immune response and avoidance of allergy. The balance between T-helper (Th)2 cells and T-regulatory (Treg) cells has a critical role in the generation of immune responses to environmental antigens. Allergic individuals display an aberrant activation and expansion of Th2 cells. It appears that aberrant activation of Th2 cells in allergy is secondary to impaired mechanisms of peripheral T-cell tolerance that is normally mediated by antigen-specific T-cell anergy, Treg cells and suppressive cytokines, IL-10 and TGF-Beta. Therefore, a most appealing therapy for allergic diseases would be an allergen-specific immunotherapy that reduces Th2 cytokine production and promotes induction of anergy, Treg and suppressor cytokines. Such novel therapeutic approaches include the use of recombinant allergen-derived peptides, recombinant DNA technology and adjuvants. These approaches are employed individually or in combination in order to induce T-cell anergy and to utilize innate immunity in order to alter the balance of Th1- and Th2-type cytokines and generate or expand Treg in vivo.
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Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass., USA.
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D000485:Allergens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D007108:Immune Tolerance; D009841:Oligonucleotides / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D016207:Cytokines; C497761:NOTCH1 protein, human; D009841:Oligonucleotides; D010455:Peptides; D051881:Receptor, Notch1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D000094632:Thymic Stromal Lymphopoietin