REGULATION OF CYTOKINE EXPRESSION BY HUMAN BLOOD BASOPHILS

IL-4 and IL-13 are key immunoregulatory cytokines because of their abi lity to induce and amplify Th2-type immune responses and by promoting IgE formation. The basophil is a particularly prominent source of IL-4 /IL-13, which are rapidly produced upon Fc epsilon RI cross-linking. C ytokine expression by basophils is unique and distinct from other cell types, since: (1) Basophils are the only cell type constitutively exp ressing IL-4 and IL-13 mRNA. IL-4/IL-13 message and protein are expres sed in a very restricted manner, since neither the mRNAs nor the prote in products of most proinflammatory Th1-type, and even Th2-type, cytok ines or chemokines are expressed; (2) Basophils secrete IL-4/IL-13 als o upon IgE-independent activation (IL-3 plus C5a), and they are thereb y potentially capable of initiating a Th2 response. Furthermore, we id entified an adjuvant from helminths capable of directly inducing IL-4 formation, and (3) IL-4 expression by basophils is resistant to counte r-regulatory effecters inhibiting Th2 development. Studies about the r egulation of IgE-dependent and -independent IL-4/IL-13 expression by d ifferent cytokines, growth factors and chemokines demonstrate that the different basophil effector functions such as chemotaxis, exocytosis, leukotriene C4 formation and cytokine expression are regulated separa tely. Thus, our study supports a key immunoregulatory role of basophil s in the skewing of immune responses to Th2.