IL-1-ALPHA AND TNF-ALPHA ARE REQUIRED FOR IL-12-INDUCED DEVELOPMENT OF TH1 CELLS PRODUCING HIGH-LEVELS OF IFN-GAMMA IN BALB C BUT NOT C57BL/6 MICE/

The development of Th1- or Th2-type responses determines the type of i mmune response that is elicited in response to Ag, Responsiveness to I L-12 is critical for the development of Th1-type CD4(+) T cells requir ed for cell-mediated immune responses, Addition of IL-12 to primary cu ltures of CD4(+) T cells stimulated with OVA and splenocytes or dendri tic cells resulted in the development of a Th1 phenotype with the capa city to secrete high levels of IFN-gamma upon restimulation with splen ic APC. The present study shows that using dendritic cells to present Ag upon restimulation reveals a requirement for additional cofactors, including IL-1 alpha and TNF-alpha, which were provided by spleen cell s but not dcedritic cells. Furthermore, these cofactors are required f or optimal IL-12-induced Th1 development in BALB/c but not C57BL/6 mic e. This differential requirement for such cofactors in IL-12 driven Th 1 development may play a role in genetic predisposition to Th1 or Th2 responses to infectious agents.