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TCR and IL-12 Receptor Signals Cooperate to Activate an Individual Response Element in the IFN- Promoter in Effector Th Cells¹

Feng Zhang^*, Tetsuo Nakamura and Thomas M. Aune^2,*

^* Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232; and Division of Medicine, Institute of Gastroenterology, Tokyo Women’s Medical College, Tokyo, Japan

IFN- 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- promoter or expressing the green fluorescent protein gene under the control of an IFN- "minigene" were employed to explore the basis for IL-12 regulation of IFN- 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- gene transcription by at least two separate mechanisms; IL-12R signaling without TCR signaling targets promoter regions outside of the 100-bp IFN- TCR-RE, and IL-12R signaling also stimulates TCR-induced activity of the proximal TCR-RE.

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