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National Laboratory of DNA Medicine, Division of Molecular and Life Science, Pohang University of Science and Technology, Hyoja Dong, Pohang, Korea
IL-12 is a pleiotropic cytokine that plays an important role
in innate and adaptive immunity. IL-12 induces T cell proliferation and
IFN-
secretion from activated T cells. It was also reported that
IL-12 prevents apoptosis of CD4+ T cells. However, the
signaling mechanism that regulates these IL-12-induced responses is
poorly understood yet. In this study, we demonstrated that IL-12
activates phosphatidylinositol 3-kinase (PI3K)/Akt pathway in murine
CD4+ T cells, and that this signaling pathway is required
for IL-12-induced T cell proliferation and antiapoptotic function, but
not for IFN- induction. Through PI3K/Akt pathway, IL-12 up-regulates
the expression of cell cycle-related molecule such as cyclin D3, and
antiapoptotic molecules such as Bcl-2 and cellular inhibitors of
apoptosis proteins-2, followed by down-regulation of active
caspase-3. These results suggest that PI3K/Akt pathway is critical for
mediating IL-12-induced CD4+ T cell responses such as T
cell proliferation and survival.
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