TCR and IL-12 receptor signals cooperate to activate an individual response element in the IFN-gamma promoter in effector Th cells.

Zhang F, Nakamura T, Aune TM
J Immunol. 1999 163 (2): 728-35

PMID: 10395664

IFN-gamma is a key regulatory cytokine of the immune system. Reporter transgenic mice expressing the luciferase gene under the control of separate TCR-response elements (TCR-RE) from the IFN-gamma promoter or expressing the green fluorescent protein gene under the control of an IFN-gamma "minigene" were employed to explore the basis for IL-12 regulation of IFN-gamma gene transcription. In the absence of TCR stimulation, IL-12 did not activate the TCR-REs but did induce green fluorescent protein expression. TCR plus IL-12R stimulation of effector Th cells resulted in: 1) enhanced activation of the proximal, but not the distal, TCR-RE, and 2) increased induction of cJun-proximal TCR-RE complexes and c-Jun protein expression. Overexpression of cJun, but not cFos, increased activity of the proximal TCR-RE in T cells. These results suggest that IL-12R signaling affects IFN-gamma gene transcription by at least two separate mechanisms; IL-12R signaling without TCR signaling targets promoter regions outside of the approximately 100-bp IFN-gamma TCR-RE, and IL-12R signaling also stimulates TCR-induced activity of the proximal TCR-RE.

MeSH Terms (21)

Animals CD3 Complex Cells, Cultured Immune Sera Immune Tolerance Interferon-gamma Interleukin-12 Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Transgenic Mitogens Nuclear Proteins Promoter Regions, Genetic Receptors, Antigen, T-Cell Receptors, Interleukin Receptors, Interleukin-12 Response Elements Signal Transduction T-Lymphocytes, Helper-Inducer

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