BALB/c mice bearing a transgenic IL-12 receptor β2 gene exhibit a nonhealing phenotype to Leishmania major infection despite intact IL-12 signaling

In BALB/c mice infected with Leishmania major, early secretion of IL-4 leads to a Th2-type response and nonhealing. We explored the role of IL-4-induced down -regulation of the IL-12R beta2 chain in the establishment of this Th2 response. First, we showed that the draining lymph nodes of resistant C57BL/6 mice infected with L. major were enriched in CD4(+)/IL-12R beta2 chain' cells producing IFN-gamma. Next, we demonstrated that BALB/c background mice bearing an IL-12R beta2-chain transgene manifested a nonhealing phenotype similar to wild-type littermates despite the persistence of their ability to undergo STAT4 activation. Finally, we found that such transgenic mice display more severe infection than wild-type littermates when treated with IL-12 7 days after infection, and under this condition, the mice display increased Leishmania Ag-Induced IL-4 secretion. These studies indicate that although CD4(+)/IL-12R beta2 chain' T cells are important components of the Th1 response, maintenance of 1L-12R beta2 chain expression is not sufficient to change a Th2 response to a Th1 response in vivo and thus to allow BALB/c mice to heal L major infection. The Journal of Immunology, 2001, 166: 6776-6783.