REGULATION OF IGE AND IGG(4) RESPONSES BY ALLERGEN-SPECIFIC T-CELL CLONES TO BEE VENOM PHOSPHOLIPASE A(2) IN-VITRO

An in vitro antibody response to bee venom phospholipase A(2) (PLA) fr om peripheral blood mononuclear cells of bee sting-sensitized individu als was achieved after stimulation with PLA and pokeweed mitogen. This stimulation resulted in a secretion of T-H1-associated cytokines and induced PLA-specific and nonspecific IgG(4) antibody production but no t IgE production. The addition of interleukin-4 (IL-4) to this system decreased the secretion of IgG antibodies, whereas secretion of polysp ecific IgE was induced. The mitogen was nor required if peripheral blo od mononuclear cells were enriched with autologous, PLA-specific, rest ing T-cell clones in the presence of the antigen. In these experiments the cytokine profile of the particular clone determined the antibody class generated. Low ratios of IL-4 to interferon-gamma, induced by th e antigen alone or obtained by neutralizing anti-IL-4 antibodies, enha nced IgG(4) antibody formation, whereas IgE levels increased at high r atios of IL-4 to interferon-gamma. These results suggest a complementa ry regulation of the main isotypes, IgE and IgG(4) implicated in aller gic and protective hyperimmune responses.