Modulation of IL-4-induced human IgE production in vitro by IFN-gamma and IL-5: the role of soluble CD23 (s-CD23).
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-gamma, IFN-alpha, 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-gamma 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-gamma 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-gamma, IFN-alpha, and PGE-2, respectively.
Pène
J
J
UNICET, Laboratory for Immunology, Dardilly, France.
Chrétien
I
I
Rousset
F
F
Brière
F
F
Bonnefoy
J Y
JY
de Vries
J E
JE
D000911:Antibodies, Monoclonal / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4; D015848:Interleukin-5; D007378:Interleukins / Q000032:analysis / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D007378:Interleukins; D007519:Isoantigens; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D015232:Dinoprostone