ALLERGEN-SPECIFIC HUMAN IGE HELPER T-CELL LINES DERIVED FROM PATIENTSALLERGIC TO JAPANESE CEDAR POLLEN

To study the regulatory mechanism of allergen-dependent human IgE synt hesis, Cryj I-specific and interleukin 4 (IL-4)-producing CD4+ T cell lines (SN-4 and SS-12) were established from 2 patients allergic to Ja penese cedar pollen who highly expressed IL-4 mRNA in T cells in respo nse to Cryj I stimulation. Upon stimulation of SN-4 and SS-12 cells wi th Cry j I, IL-4 production, which was observed at the protein and the mRNA levels, was induced in an HLA-DR-restricted manner, using autolo gous and allogeneic antigen-presenting cells. In addition to IL-4, not only considerable amounts of IL-5 and IL-6 but also very small amount s of IL-2 and interferon-gamma (IFN-gamma) were secreted by SN-4 and S S-12 cells, indicating that they fit into the Th2-1ike phenotype. The culture supernatant from Cry j I-activated SN-4 cells had the ability to induce IL-4-dependent IgE synthesis, CD23 expression and soluble CD 23 release. Moreover, Cry j I-dependent IgE synthesis medated by SN-4 cells derived from 1 patient expressing HLA-DRw8, w9 could be specific ally induced in both autologous and HLA-DRw9-matched allogeneic B cell cultures. This IgE induction was inhibited by neutralizing,o antibodi es to IL-4, IL-5 and IL-6, but was not enhanced by anti-IFN-gamma anti body. On the other hand, neither IL-4 production nor IgE synthesis was induced when SN-4 cells were cocultured in the presence of Cry j I wi th HLA-DRw8-matched or histoincompatible allogeneic cells. A similar r esult was obtained with HLA-DR4-restricted SS-12 cells generated from another patient with HLA-DR4, w13. These data demonstrate that allerge n-reactive and HLA-DR-restricted CD4+ T cells with the Th2 phenotype s uch as SN-4 and SS-12 cells specific for Cry j I are responsible for t he induction and enhancement of IgE synthesis through the absolute pro duction of Th2-specific cytokines.