INTERLEUKIN (IL)-4-INDEPENDENT INDUCTION OF IMMUNOGLOBULIN (IG)E, ANDPERTURBATION OF T-CELL DEVELOPMENT IN TRANSGENIC MICE EXPRESSING IL-13

Recent studies using interleukin (IL)-4-deficient animals have highlig hted the existence of ILL-4-independent immunoglobulin (Ig)E induction . We have established transgenic mice expressing IL-13 from a transgen e comprising a genomic fragment containing the IL-13 gene and the huma n CD2 locus control region. The transgenes were expressed in lymphoid tissues and induced by T cell activators, suggesting regulation by ele ments of the IL-13 promoter. IL-13 transgenic lines expressed 10-100-f old higher levels of serum IgE than their littermate controls, but had normal levels of other serum Ig isotypes. Elevated IgE levels were al so detected in sera from IL-4-deficient mice carrying IL-13 transgenes , indicating that IL-4 is not required for IL. 13-induced IgE expressi on in the mouse. Expression of IL-13 also perturbed the development of thymocytes. Although thymocyte development was normal up to 4 wk of a ge, thymocyte number decreased dramatically thereafter, reaching 10% o f normal by 10 wk, and despite normal size and appearance, histologica l examination demonstrated that transgenic thymi contained only small foci of thymocytes. The reduction in thymocyte number was due mainly t o a depletion of CD4(+)CD8(+) thymocytes, and did not affect significa ntly the composition of peripheral T cell populations. These data indi cate that expression of IL-13 transgenes in vivo can regulate IgE prod uction in the mouse, and that IL-13 may also influence thymocyte devel opment.