Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis.
Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.
Selmaj
K
K
Department of Neurology, Laboratory of Neuroimmunology,Medical Academy of Lodz, 22, Kopcinskiego Street, 90-153, Lodz, Poland.
Kowal
C
C
Walczak
A
A
Nowicka
J
J
Raine
C S
CS
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003587:Cytomegalovirus / Q000235:genetics; D003601:Cytotoxicity Tests, Immunologic; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D016233:Immunotherapy, Active; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology; D019444:Vaccines, DNA / Q000276:immunology*
D001324:Autoantigens; D018991:Myelin Proteolipid Protein; D019444:Vaccines, DNA