Human Peripheral Blood Basophlh Primed by Iuterleuk;n 3 (ID3) Produce II.,4 in Response to hnmunoglobulln E Receptor Stimulation

S u m m a r y In contrast to most cytokines, interleukin 4 (II_,4) expression is restricted to T lymphocytes, with the exception of mast cell lines and mast cells, as more recently demonstrated in rodents. Little is known, however, about the capacity of human nonlymphoid cells to produce I1,4. In this study we show that mature human basophils are capable of expressing I1-4 and examine the regulation of I1.,4 production in comparison with the lipid mediator leukotriene C4. 11-4 was produced upon immunoglobulin E receptor (IgER) activation of basophils cultured with Ib3, a cytokine previously shown to prime these cells for enhanced release of inflammatory mediators. In some experiments, I1-3 or IgER activation alone also induced I1-4 production close to the detection limit. The effect of IL-3 on IgER-dependent I1,4 expression was dose and time dependent: maximal I1-4 production occurred between 18 and 48 h preexposure of basophils to 3-10 ng/ml I1.-3. IgER-induced I1.-4 synthesis and release by basophils cultured with Ib3 was rapid and complete after 6 h. In contrast to I1,3, other cytokines (I1,5, granulocyte/macrophage colony-stimulating factor, and nerve growth factor) that also prime basophils for enhanced histamine and leukotriene C4 release did not promote IgER-induced I1,4 synthesis. Basophils appear to secrete a "TH2like" cytokine profile since no detectable I1,2 or interferon 3' was produced upon IgER activation. Mononuclear cells (depleted of basophils), cultured in parallel, did not release I1-4 in response to I1-3 and/or IgER activation, and produced approximately ten times less I1-4 than basophils upon nonspecific activation by phorbol ester and calcium ionophore. Thus, human basophils are an important cellular source of I1-4, and may, therefore, in addition to their inflammatory effector functions, also regulate the differentiation of T helper cells and B cells, in particular in allergic diseases.