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Alterations in transcription factor binding in anergized human CD4+T- lymphocytes Heisel, Olaf


Background: The mechanisms responsible for the induction of human clonal anergy are not well understood. We have utilized an in vitro model of human T-cell anergy to explore the perturbations in cell signaling at the level of IL-2 gene transcription, and to define the contribution of other cytokines to this effect. Methods: An in vitro model of clonal anergy was established using peripheral T-lymphocytes from healthy human donors. CD4+ T-cells were anergized by pre-stimulation with an anti-CD3 mAb followed by restimulation 72 hours later with anti-CD3 with or without anti-CD28. Proliferation was measured by [3H]- thymidine incorporation and IL-2 production using ELISA. Results: CD4+ T-cells anergized with OKT3 displayed a marked reduction in proliferation (P=0.0036) and IL-2 production (P

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