THE RELATIVE CONTRIBUTION OF IL-4 AND IL-13 TO HUMAN IGE SYNTHESIS INDUCED BY ACTIVATED CD4(-CELLS() OR CB8(+) T)

The relative contribution of IL-4 and IL-13 to the regulation of IgE s ynthesis has remained relatively poorly characterized, partially becau se of lack of suitable animal models. We have studied the roles of IL- 4 and IL-13 in human IgE synthesis induced by supernatants derived fro m activated CD4(+) or CD8(+) T cell clones. Neutralizing anti-IL-4 and anti-IL-13 monoclonal antibodies (mAbs) inhibited IgE synthesis induc ed by anti-CD40 mAbs and supernatants from CD4(+) T cells by an averag e 61% and 42%, respectively (n = 25). Recombinant IL-13 had additive e ffects on IL-4-induced IgE synthesis, but only when IL-4 was present a t low concentrations. Accordingly, IL-4 was the dominant IgE synthesis -inducing cytokine derived from highly polarized T helper (TH)(2) cell s. However, anti-IL-13 mAbs also significantly inhibited IgE synthesis induced by two of three supernatants derived from allergen-specific T -H2-like cell lines generated from the skin of patients with atopic de rmatitis. Furthermore, anti-IL-13 mAbs almost completely inhibited IgE synthesis induced by supernatants from T-H1 cells or CD8(+) T cell cl ones. Taken together, these data indicate that IL-13, in addition to I L-4, contributes to IgE synthesis induced by all T helper cell subsets , including allergen-specific T-H2 cells. Moreover, IL-13 appears to b e the major IgE synthesis-inducing cytokine derived from T-H1 cells or CD8(+) T cells.