New insights into the mechanisms which regulate IgE synthesis in man

The studies summarized here provide further insight into the cellular and molecular mechanisms involved in the regulation of human IgE synthesis. They clearly demonstrate that IL-4 is the essential factor for induction of human IgE synthesis, since no substantial in vitro IgE production can be obtained in the absence of this lymphokine. Another T cell-derived lymphokine, IFN-gamma, negatively regulates the IgE synthesis induced by IL-4. These two lymphokines can be produced by different T helper cells, but they can also represent the product of the same T cell clone (TCC). In this case, the possibility that a given TCC provides helper function for IgE seems to be dependent upon the balance between the amounts of the two lymphokines produced. Additional cellular and/or molecular signals are involved in IL-4-dependent IgE synthesis. First of all, a direct T-B interaction is required to precede the activity of IL-4. This interaction does not necessarily consist of cognate interaction between T and B cells, as occurs for IgE synthesis induced by alloreactive TCC. In the presence of exogenous IL-4 virtually all CD4+, and even a number of CD8+, TCC can provide the signaling required by B cells to synthesize IgE. An interaction between some adhesion molecule, more expressed on activated than resting T cells, and its receptor on B cells is sufficient to prepare resting B cells to synthesize IgE in response to IL-4. Furthermore, T cells also contribute to IL-4-dependent IgE synthesis by releasing IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)