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Autocrine activation by interferon‐γ of STAT factors following T cell activation
Author(s) -
Girdlestone John,
Wing Mark
Publication year - 1996
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830260329
Subject(s) - autocrine signalling , biology , jurkat cells , stat1 , microbiology and biotechnology , tumor necrosis factor alpha , t cell , cytokine , interferon gamma , transcription factor , cycloheximide , signal transduction , immunology , receptor , immune system , biochemistry , protein biosynthesis , gene
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)‐ϰB 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‐α, and interferon (IFN)‐γ 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 h 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‐γ, but not other cytokines tested, blocked activation of the factor almost completely, and IFN‐γ was found in the culture supernatants of stimulated cells at levels at which recombinant IFN‐γ could activate the factor in naive cells. Therefore, a STAT1 transcription factor is activated by IFN‐γ synthesized and released upon stimulation of T lymphocyte populations. While Jurkat cells both secret and respond to IFN‐γ in an autocrine loop, it seems likely that the responding cells may differ from those synthesizing this cytokine in the mononuclear cell cultures in the light of the recent report that Th1 cells lack the IFN‐γ receptor chain necessary for activation of STAT1 (Pernis, A., Gupta, S., Gollob, K. J., Garfein, E., Coffman, R. L., Schindler, C., and Rothman, P., Science 1995. 269 : 245).