Novel fundamental approaches to intervening in IgE-mediated allergic diseases.
Recent progress in our understanding of the immunologic basis of allergic diseases has suggested that enhanced production of the cytokines IL-4 and IL-13 by allergen-specific T cells is responsible for increased IgE synthesis and the development of allergic disease in certain individuals. Based on these observations, it is clear that approaches to inhibition of allergen-specific IgE synthesis should be aimed at blocking the activation or preventing the synthesis of IL-4 and IL-13. In the present review, two approaches toward this goal are discussed. First, an IL-4 mutant protein is described that acts as a powerful antagonist of both IL-4 and IL-13 activity, including induction of IgE synthesis by these cytokines in vitro. Second, it is demonstrated that T-cell clones can be rendered non-responsive following incubation with allergen-derived peptides representing minimal T-cell activation-inducing epitopes. These non-responsive T cells fail to produce IL-4 and IL-13 and to proliferate following subsequent activation with the relevant allergen and antigen-presenting cells. In addition, these non-responsive T cells fail to provide B-cell help for IgE synthesis. It is tempting to speculate that induction of non-responsiveness in allergen-specific T-cell clones by allergen-derived immunogenic peptides may provide the basis for successful desensitization of allergic patients.
de Vries
J E
JE
DNAX Research Institute, Human Immunology Department, Palo Alto, California 94303-1104.
D003888:Desensitization, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D007073:Immunoglobulin E / Q000378:metabolism / Q000502:physiology*; D007377:Interleukin-3 / Q000378:metabolism / Q000502:physiology; D015847:Interleukin-4 / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology
D007377:Interleukin-3; D015847:Interleukin-4; D007073:Immunoglobulin E