Il-2 Gene-Expression and Nf-Kappa-B Activation Through Cd28 Requires Reactive Oxygen Production by 5-Lipoxygenase

• Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase Az and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-KB activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Keyword

cd28

costimulation

human monocytes

il-2

lymphocytes-t

mediated suppression

molecule cd28

nf-kappa-b

nuclear factor

pathway

receptor

roi

t-cell activation

transcription

tumor-necrosis-factor

Publication and Content Type

ref (subject category)

art (subject category)