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

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.