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PEI – a potent, but not harmless, mucosal immuno-stimulator of mixed T-helper cell response and FasL-mediated cell death in mice

Gene Therapy volume 10, pages 1575–1583 (2003)Cite this article

Abstract

Polyethyleneimine (PEI) is one of the most effective gene delivery systems available today. However, very little is known about its ability to stimulate a systemic immune response and the molecular mechanisms thereof. However, this information is vital for the future development of new gene delivery systems.

Here we address this issue by studying gene expression profiles from spleen lymphocytes after in vivo immunization of mice with PEI formulated with a reporter plasmid (PEI+) or the formulation alone (PEI−). PEI− was found to provoke the activation of genes with important immunostimulatory functions, but without the necessary costimulatory signals. PEI+ resulted in: a mixed Th1/Th2 response; activation of both CD8+ and CD4+ T cells, with a larger effect on CD4+; and FasL-mediated antigen-induced cell death. A comparison of the immune responses of PEI+ with that of the clinically used tetanus toxoid–aluminum phosphate vaccine showed that the DNA vaccine provoked a stronger immune response as compared to the protein vaccine. However, many genes involved in other cellular responses such as apoptosis, stress responses and oncogenesis were activated in PEI+, supporting the theory of immunostimulation by danger genes, but also pointing toward possible adverse reactions such as Alzheimer's disease.

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Acknowledgements

We thank Dr. Diane Burgess, Department of Pharmacy, University of Connecticut for helpful comments. This work was supported by the Swedish Board for Technical Development Grant p11381-1, the Swedish National Network for Drug Development Grant B 6 3368/98 and the Swedish Research Council Grant 621-2001-3563.

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  1. Department of Pharmacy, Uppsala University, Uppsala, Sweden

    K Regnström, E G E Ragnarsson, M Köping-Höggård, E Torstensson, H Nyblom & P Artursson

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Regnström, K., Ragnarsson, E., Köping-Höggård, M. et al. PEI – a potent, but not harmless, mucosal immuno-stimulator of mixed T-helper cell response and FasL-mediated cell death in mice. Gene Ther 10, 1575–1583 (2003). https://doi.org/10.1038/sj.gt.3302054

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