Antigen mediated and polyclonal stimulation of human cytokine production elicit qualitatively different patterns of cytokine gene expression
Abstract
Polyclonal activators are widely used as surrogate antigens in analysis of human cytokine gene expression. An implicit assumption is that the T cell activation and cytokine production observed in response to polyclonal activation provides a more intense, but qualitatively identical, reflection of results that would be obtained with antigen. Here we demonstrate that stimulation using accessory cell independent (immobilized anti-CD3 mAb) or dependent [phytohemagglutinin (PHA) or soluble anti-CD3 mAb] polyclonal activators yields different conclusions from those that are obtained in response to antigen-specific T cell activation. Cytokine synthesis in 1-5 day bulk cultures of fresh peripheral blood mononuclear cells (PBMC) from 52 subjects evenly divided between grass pollen sensitive allergic rhinitis subjects and normal, non-atopic controls were examined. Antigen-specific re-stimulation elicited elevated IL-4 and IL-10 production and lower IFN-gamma synthesis among allergic subjects than normal non-atopic control subjects. This commitment of fresh PBMC towards a Th2-like response in atopics and the dominance of the IFN-gamma response seen in non-allergic subjects was reinforced when the ratio of IFN-gamma:IL-4 production in bulk...Continue Reading
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