Science · 1989 · 891 citations · 34 references
Life SciencesImmunologyMolecular BiologyCell SignalingCellular ImmunologySignal TransductionCytokine BiologyCytokine RegulationCytokine SignalingImmune Cell SignalingT Cell ActivationT Cell BiologyCell ActivationCytokine Expression RegulationMessenger Rna Half-lifeMessenger Rna TurnoverRegulation Of T-cell ActivationSignal Transduction In T CellsT Cell Activation CytokinesT-cell Mediated Responses
Quiescent T cells upregulate many genes upon mitogen or antigen stimulation, but the mRNAs of some induced genes are rapidly degraded compared to constitutively expressed mRNAs. Stimulation of the CD28 surface molecule activates a pathway that specifically regulates the stability of mRNAs encoding interleukin‑2, interferon‑γ, tumor necrosis factor‑α, and granulocyte‑macrophage colony‑stimulating factor. This CD28‑dependent pathway selectively alters the degradation of these lymphokine mRNAs without affecting the steady‑state levels, transcription, or half‑lives of other activation genes, showing that surface signals can modulate gene expression through targeted mRNA decay.
Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-γ, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c- myc , c- fos , IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.
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Daniel Caput, Bruce Beutler, K. Hartog et al. · Proceedings of the National Academy of Sciences · 1986 · 1.5K citations · Full text
Two types of mouse helper T-cell clone
Tim R. Mosmann, Robert L. Coffman · Immunology Today · 1987 · 806 citations