The alternative NF-kappaB signalling pathway is a prerequisite for an appropriate immune response against lymphocytic...

Two major nuclear factor-kappaB (NF-kappaB) signalling pathways are involved in the regulation of the immune response. While the classical NF-kappaB pathway is responsible for regulation of genes encoding components of the innate immune response, the alternative NF-kappaB signalling pathway mediates processes of the adaptive immune system. To evaluate the role of the NF-kappaB signalling pathways in the control of viral infection, we have used lymphocytic choriomeningitis virus (LCMV) infection of mice, which is known to be an excellent model for studying antiviral immune responses. Via the use of mice that were deficient in NF-kappaB subunits from either the classical (p50(-/-) mice) or the alternative NF-kappaB pathway (p52(-/-) mice), we were able to demonstrate that the alternative NF-kappaB pathway is required for the T-cell-mediated immune response against LCMV. Mice that were deficient in the alternative NF-kappaB pathway subunit p52 showed an impaired T-cell response against LCMV infection. Furthermore, these mice also showed an impaired T-cell-dependent humoral immune response against vesicular stomatitis virus (VSV) infection. Adoptive transfer experiments revealed that impaired priming, but not the T-cell response itself, was responsible for the defective cellular immune response against LCMV infection. Our data demonstrate that a functional alternative NF-kappaB signalling pathway is required to assure an adequate immune response after viral infection.