NF-kappa B2 is required for optimal CD40-induced IL-12 production but dispensable for Th1 cell differentiation

NF-kappa B is a ubiquitously expressed transcription factor involved in the regulation of innate and adaptive immunity. As part of studies to define the role of various NF-kappa B family members in Th cell development and maintenance, we infected NF-kappa B2(-/-) and control mice with Leishmania major and followed disease progression. NF-kappa B2(-/-) mice on a normally resistant background develop chronic nonhealing lesions associated with uncontrolled parasite replication and a failure to develop an IFN-gamma response. We show that there are no intrinsic defects in Th cell differentiation in the absence of NF-kappa B2. Indeed, NF-kappa B2(-/-) T cells are able to develop a Th1 phenotype and protect recombination-activating gene(-/-) mice from progressive cutaneous leishmaniasis. We demonstrate instead that the susceptibility of NF-kappa B2(-/-) mice to L. major is the result of an IL-12 deficiency, and we provide evidence for a specific impairment in CD40-induced IL-12 production by macrophages lacking this transcription factor.