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Antigen mediated and polyclonal stimulation of human cytokine production elicit qualitatively different patterns of cytokine gene expression

作者:Mie Imada, F. Estelle R. Simons, Francis T. Jay, Kent T. HayGlass · 发表于:International Immunology · 年份:1995 · DOI:10.1093/intimm/7.2.229 · 被引用次数:50 · 研究领域:Immune Cell Function and Interaction

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 culture was examined. Atopic individuals exhibited median IFN-gamma:IL-4 values of 0.07, whereas grass pollen stimulated cytokine production by normal subjects yielded a ratio of 4.8. In marked contrast, IL-2, IL-4, IL-10 and IFN-gamma production elici...