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and TNF- Are Required for IL-12-Induced Development of Th1 Cells Producing High Levels of IFN-
in BALB/c But Not C57BL/6 Mice1
*
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA 94303;
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110; and
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104
The development of Th1- or Th2-type responses determines the type
of 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+ T
cells stimulated with OVA and splenocytes or dendritic cells resulted
in the development of a Th1 phenotype with the capacity to secrete high
levels of IFN-
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-1
and
TNF-, which were provided by spleen cells but not dendritic cells.
Furthermore, these cofactors are required for optimal IL-12-induced Th1
development in BALB/c but not C57BL/6 mice. This 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.
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