Modulation of IL‐4‐induced human IgE production in vitro by IFN‐γ and IL‐5: The role of soluble CD23 (s‐CD23)

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Abstract
IL‐4 specifically induced IgE production by peripheral blood lymphocytes or by tonsil or spleen cells from healthy donors. IL‐4‐induced IgE synthesis was dependent on CD4+ T cells and monocytes and was blocked by IFN‐γ, IFN‐α, and prostaglandin E‐2 (PGE‐2). These substances also inhibited IL‐4‐induced CD23 expression and subsequent release of soluble CD23 (s‐CD23). In addition, IgE production was blocked by F(ab′)2 fragments of an mAb against CD23. In contrast, IL‐5 enhanced IL‐4‐induced IgE production, provided IL‐4 was added at nonsaturating concentrations. This increase in IgE production correlated quantitatively with an enhanced release of s‐CD23. Collectively, these results indicate that there is a correlation between s‐CD23 release and IgE production. However, s‐CD23 fractionated from supernatants of the lymphoblastoid cell line RPMI‐8866 was ineffective in inducing IgE production in the absence of IL‐4, but acted synergistically with suboptimal concentrations of IL‐4. In addition, it is demonstrated that alloreactive T‐cell clones produced varying concentrations of IL‐4, IL‐2, or IFN‐γ upon stimulation. Only supernatants of 2/4 of these T‐cell clones induced a low degree of IgE synthesis, but in the presence of anti‐IFN‐γ antibodies, all four supernatants induced a strong induction of IgE production. This IgE synthesis was blocked specifically by anti‐IL‐4 antibodies, indicating that IL‐4 is the sole inducer of IgE synthesis. Our findings demonstrate that IL‐4‐induced IgE production involves complex interactions of T cells, B cells, and monocytes and is positively modulated by IL‐5 and s‐CD23 but down‐regulated by IFN‐γ, IFN‐α, and PGE‐2, respectively.

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