IL-1α and TNF-α are required for IL-12-induced development of Th1 cells producing high levels of IFN-γ in BALB/c but not C57BL/6 mice

The development of Th1- or Th2-type responses determines the type of the immune response that is elicited in response to Ag. Responsiveness to IL-12 is critical for the development of Th1-type CD4⁺ T cells required for cell- mediated immune responses. Addition of IL-12 to primary cultures of CD4⁺ cells stimulated with OVA and splenocytes or dendritic cells resulted in the development of a Th1 phenotype with the capacity of secrete high levels of IFN-γ upon restimulation with splenic APC. The present study shows that using dendritic cells to present Ag upon restimulation reveals a requirement for additional cofactors, including IL-1α and TNF-α, which were provided by spleen cells but no dendritic cells. Furthermore, these cofactors are required for optimal IL-12-induced Th1 development in BALB/c but not C57BL/6 mice. The differential requirement for such cofactors in IL-12-driven Th1 development may play a role in genetic predisposition to Th1 or Th2 responses to infectious agents.