title: Polyclonal and clonal analysis of human CD4+ T-lymphocyte responses to nut extracts.
abstract: The induction of IgE antibodies to aeroallergens depends upon antigen-specific CD4+ helper T cells of an 'interleukin-4 (IL-4)-dominant' phenotype. Nuts also drive IgE-mediated hypersensitivity and are the most dangerous of the orally encountered allergens. We have studied the polyclonal T-cell responses of atopic and non-atopic individuals to extracts of peanut, brazilnut and hazelnut. Strong proliferative responses were observed in all patients but specific IgE was only present in the nut-allergic patients suggesting a similar pathogenic mechanism to aeroallergen-mediated hypersensitivity. To investigate this hypothesis a panel of peanut-reactive T-cell clones was raised from a peanut- and brazilnut-allergic individual without hazelnut allergy. The antigen specificity, major histocompatibility complex (MHC) class II restriction and cytokine profiles of the T-cell clones were determined. With the exception of one T-cell clone, which proliferated in response to both peanut and hazelnut extract, the peanut T-cell clones were not cross-reactive with hazelnut or brazilnut. The T-cell clones recognized antigen in association with HLA-DR and HLA-DP but not HLA-DQ class II molecules. The peanut-specific clones produced high levels of IL-4 and low levels of interferon-gamma (IFN-gamma), exhibiting the 'TH2-like' profile which dominates the aeroallergen response. In contrast, the T-cell clone that was cross-reactive on both peanut and hazelnut allergen had a Th0-like phenotype, consistent with the lack of specific serum IgE to hazelnut. These results support the importance of functionally distinct T-cell populations that recognize oral allergens. The relative production of IL-4 and IFN-gamma of the cloned T cells in the peanut-allergic patients plays a role in determining whether or not IgE antibody responses are induced with the associated potential to develop anaphylactic reactions.
authors.affiliation: Department of Immunology, St Mary's Hospital Medical School, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Higgins
authors.forename: J R
authors.initials: JR
authors.lastname: Lamb
authors.forename: R A
authors.initials: RA
authors.lastname: Lake
authors.forename: R E
authors.initials: RE
authors.lastname: O'Hehir
mesh_terms: D000328:Adult; D000485:Allergens / Q000009:adverse effects* / Q000276:immunology; D010367:Arachis / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D000939:Epitopes / Q000032:analysis; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology*; D006682:HLA-DP Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D009754:Nuts / Q000009:adverse effects* / Q000276:immunology
chemical_list: D000485:Allergens; D000939:Epitopes; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma