title: IL-12 provides proliferation and survival signals to murine CD4+ T cells through phosphatidylinositol 3-kinase/Akt signaling pathway.
abstract: IL-12 is a pleiotropic cytokine that plays an important role in innate and adaptive immunity. IL-12 induces T cell proliferation and IFN-gamma 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-gamma 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.
authors.affiliation: National Laboratory of DNA Medicine, Division of Molecular and Life Science, Pohang University of Science and Technology, Hyoja Dong, Pohang, Korea.
authors.forename: Jae Kwang
authors.initials: JK
authors.lastname: Yoo
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Lee
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D056743:Cyclin D3; D016213:Cyclins; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma; D018664:Interleukin-12; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C534697:Ccnd3 protein, mouse