Generation of a protective T cell response following viral infection of the CNS is independent of either IL-12 or IL-23

Abstract The functional role of IL-12 and IL-23 in generating effector T cells following viral infection of the central nervous system (CNS) was determined. Instillation of mouse hepatitis virus (MHV) into the CNS of C57BL/6 mice results in an acute encephalitis followed by a chronic demyelinating disease. MHV-infected mice express mRNA transcripts specific for IL-12p35 and IL-23p19 subunits within the brains. Antibody-mediated blocking of IL-23 (anti-IL-23p19) or IL-12 and IL-23 (anti-IL-12/23p40) did not reduce numbers of virus-specific T cells and treated mice cleared virus from the CNS demonstrating that blocking IL-23 does not affect the generation of a Th1 response. Therapeutic administration of anti-IL-23p19 to infected mice with established demyelination did not attenuate disease indicating IL-23 does not contribute to viral-induced demyelination. Treatment with anti-IL-12/23p40 or anti-IL-23p19 resulted in inhibition of EAE, an autoimmune model of demyelination highlighting the importance of IL-23 in CNS autoimmune inflammation and disease. These data indicate that i) IL-12 and IL-23 signaling are dispensable in generating a protective response following CNS infection with MHV and ii) IL-23 amplifies disease in a model of autoimmune demyelination. Therefore, targeting of IL-23 for the treatment of autoimmune diseases may offer unique advantages by reducing disease severity without muting protective responses following viral infection.