Abstract
The activation of T cells requires engagement of the T cell receptor/CD3 complex and co-stimulatory molecules, and results in the triggering of several signaling pathways which lead rapidly to the nuclear translocation of several transcription factors, such as nuclear factor (NF)-kappa B and NF-AT. A result of this activation process is the induction of a number of genes, including those encoding cytokines such as interleukin-2, tumor necrosis factor-alpha, and interferon (IFN)-gamma which have important immunoregulatory effects. We report here that a DNA-binding factor containing STAT1 also becomes activated in human peripheral blood T lymphocytes or Jurkat cells, although not until 1-2 h after stimulation. Activation is delayed a further 1-2 hr when mononuclear cell cultures are stimulated by an antigen which requires processing. Appearance of the STAT1 factor is significantly reduced in the presence of cyclosporin A, and blocked by cycloheximide, indicating that its activation is dependent upon a protein(s) synthesized in response to initial signaling events. Neutralizing antiserum against IFN-gamma, but not other cytokines tested, blocked activation of the factor almost completely, and IFN-gamma was found in the culture sup...Continue Reading
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