PEI - a potent, but not harmless, mucosal immuno-stimulator of mixed T-helper cell response and FasL-mediated cell death in mice.
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.
Regnström
K
K
Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Ragnarsson
E G E
EG
Köping-Höggård
M
M
Torstensson
E
E
Nyblom
H
H
Artursson
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053222:Fas Ligand Protein; D015870:Gene Expression; D015316:Genetic Therapy / Q000009:adverse effects* / Q000379:methods; D007114:Immunization; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011094:Polyethyleneimine / Q000009:adverse effects*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D019444:Vaccines, DNA / Q000009:adverse effects*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D011094:Polyethyleneimine