Bee venom phospholipase A2‐specific T cell clones from human allergic and non‐allergic individuals: cytokine patterns change in response to the antigen concentration

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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 α,β T cell receptor. Depending on the T cell clone, maximal stimulation required 1 to 100 μg/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-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor. Most clones also produced tumor necrosis factor α (TNF-α) and tumor necrosis factor β (TNF-β), 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 producedbut little or not IFN-γ, whereas at higher PLA concentrations significant amounts of both IL-4 and IFN-γ were obtained. Thus, these PLA-specific Tcell clones could be classified according to the changes in the ratio of IL-4/IFN-γ production in response to increasing antigen concentrations. Clones derived from allergic and hyposensitized individuals required higher critical amounts of antigen for IFN-γ induction, and expressed increasing IL-4/IFN-γ ratios with increasing concentrations of PLA. Modulation of cytokine patterns by thedose of the antigen may be a driving force for IgE or IgG formation resulting in allergy or immunoprotection.

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