title: Bee venom phospholipase A2-specific T cell clones from human allergic and non-allergic individuals: cytokine patterns change in response to the antigen concentration.
abstract: Protein antigens with both allergenic and immunoprotective properties represent appropriate molecules to study IgE and IgG regulation. We have established a panel of T cell clones specific to bee venom phospholipase A2 (PLA) from human individuals allergic, hyposensitized or immune (protected) to bee sting. All clones obtained were CD3+, CD4+ and expressed alpha, beta T cell receptor. Depending on the T cell clone, maximal stimulation required 1 to 100 micrograms/ml of PLA, and the addition of interleukin (IL)-2 and/or IL-4 increased their antigen-dependent proliferation. Following antigen stimulation, the clones produced IL-4, interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor. Most clones also produced tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor beta (TNF-beta), and some produced IL-5 and/or IL-2. Both absolute and relative amounts of secreted cytokines depended on the antigen concentration. At low antigen doses, IL-4 was produced but little or not IFN-gamma, whereas at higher PLA concentrations significant amounts of both IL-4 and IFN-gamma were obtained. Thus, these PLA-specific T cell clones could be classified according to the changes in the ratio of IL-4/IFN-gamma production in response to increasing antigen concentrations. Clones derived from allergic and hyposensitized individuals required higher critical amounts of antigen for IFN-gamma induction, and expressed increasing IL-4/IFN-gamma ratios with increasing concentrations of PLA. Modulation of cytokine patterns by the dose of the antigen may be a driving force for IgE or IgG formation resulting in allergy or immunoprotection.
authors.affiliation: Swiss Institute of Allergy and Asthma Research, Davos.
authors.forename: J M
authors.initials: JM
authors.lastname: Carballido
authors.forename: N
authors.initials: N
authors.lastname: Carballido-Perrig
authors.forename: G
authors.initials: G
authors.lastname: Terres
authors.forename: C H
authors.initials: CH
authors.lastname: Heusser
authors.forename: K
authors.initials: K
authors.lastname: Blaser
mesh_terms: D001514:Bee Venoms / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007299:Insect Bites and Stings / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D010741:Phospholipases A / Q000276:immunology*; D054467:Phospholipases A2; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001514:Bee Venoms; D016207:Cytokines; D006681:HLA-D Antigens; D015848:Interleukin-5; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010741:Phospholipases A; D054467:Phospholipases A2