Differential Transcription Directed by Discrete Gamma Interferon Promoter Elements in Naive and Memory (Effector) CD4 T Cells and CD8 T Cells

Abstract

Acquisition of the ability to produce gamma interferon (IFN-γ) is a fundamental property of memory T cells and enables one subset (T helper 1 [TH1]) to deliver its effector functions. To examine regulation of IFN-γ gene expression in a model system which recapitulates TH1 differentiation, we prepared reporter transgenic mice which express the luciferase gene under the control of proximal and distal regulatory elements (prox.(IFNγ) and dist.(IFNγ) from the IFN-γ promoter. Memory T cells, but not naive T cells, secreted IFN-γ and expressed both prox.(IFNγ) and dist.(IFNγ) transcriptional activities. Naive T cells required priming to become producers of IFN-γ and to direct transcription by these elements. While both CD4 + and CD8 + T cells produced IFN-γ, only CD4 + T cells expressed prox.(IFNγ) transcriptional activity. Induction of transcriptional activity was inhibited by known antagonists of effector T-cell populations. Cyclosporin A inhibited transcriptional activity directed by both elements in effector T cells. Elevated cyclic AMP inhibited transcriptional activity directed by prox.(IFNγ) in primed CD4 + T cells but enhanced transcriptional activity directed by dist.(IFNγ) in primed CD8 + T cells. Taken together, these data show that prox.(IFNγ) and dist.(IFNγ) transcriptional activities mirror IFN-γ gene expression in naive and memory CD4 + T cells but suggest that differences exist in regulation of IFN-γ gene expression in CD4 + and CD8 + T-cell subsets.