Susceptibility to Leishmania major in IL-4 transgenic mice is not correlated with the lack of a Th1 immune response

IL-4 transgenic mice of C3H genetic background expressing IL-4 under the control of an MHC class I promoter were infected with Leishmania major and the immune response was assessed. In contrast to littermate control mice, the transgenic mice were unable to restrict the growth of the parasites as shown by the strong increase in footpad swelling and parasite numbers in the spleen. The observed susceptibility was markedly less severe than that observed in BALB/c mice. Restimulation of lymph node cells with L. major antigen in vitro and subsequent analysis of cytokine secretion revealed that, in contrast to BALB/c mice, the cells from the IL-4 transgenic mice secreted more IL-5 and similar amounts of IFN-gamma as did the cells from litter mate control mice. These results demonstrate that the transgenic expression of IL-4 in vivo leads to the generation of more Th2 cells without affecting the generation of IFN-gamma-producing Th1 cells. This indicates that under certain conditions Th1 and Th2 immune responses during infection with L. major are not mutually exclusive, and that other factors besides the secretion of IL-4 determine whether only a Th1 or a Th2 immune response develops. The observed susceptibility of IL-4 transgenic mice to L. major was not due to the lack of IFN-gamma production but presumably to the transgenic and Th2 cell-derived IL-4 counteracting the otherwise protective effect of IFN-gamma on infected macrophages. Our results might help explain why humans develop cutaneous leishmaniasis even though IFN-gamma-producing cells are readily detectable in the lesions.