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Titolo:
Presence of CpG DNA and the local cytokine milieu determine the efficacy of suppressive DNA vaccination in experimental autoimmune encephalomyelitis
Autore:
Lobell, A; Weissert, R; Eltayeb, S; Svanholm, C; Olsson, T; Wigzell, H;
Indirizzi:
Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-17177 Biol, S-17177 Stockholm, Sweden Karolinska Hosp, Ctr Mol Med, Neuroimmunol Unit, S-10401 Stockholm, SwedenKarolinska Hosp Stockholm Sweden S-10401 Unit, S-10401 Stockholm, Sweden
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 9, volume: 163, anno: 1999,
pagine: 4754 - 4762
SICI:
0022-1767(19991101)163:9<4754:POCDAT>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTOR; MYELIN BASIC-PROTEIN; NECROSIS-FACTOR-ALPHA; BACTERIAL-DNA; T-CELL; IMMUNOSTIMULATORY DNA; EXPRESSION CASSETTES; IMMUNE ACTIVATION; PLASMID DNA; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Lobell, A Karolinska Inst, Ctr Microbiol & Tumor Biol, Box 280, S-17177 Stockholm, Sweden Karolinska Inst Box 280 Stockholm Sweden S-17177 ckholm, Sweden
Citazione:
A. Lobell et al., "Presence of CpG DNA and the local cytokine milieu determine the efficacy of suppressive DNA vaccination in experimental autoimmune encephalomyelitis", J IMMUNOL, 163(9), 1999, pp. 4754-4762

Abstract

We here study the adjuvant properties of immunostimulatory DNA sequences (ISS) and coinjected cytokine-coding cDNA in suppressive vaccination with DNA encoding an autoantigenic peptide, myelin basic protein peptide 68-85, against Lewis rat experimental autoimmune encephalomyelitis (EAE), EAE is an autoaggressive, T1-mediated disease of the CNS, ISS are unmethylated CpG motifs found in bacterial DNA, which can induce production of type 1 cytokines in vertebrates through the innate immune system. Because ISS in the plasmid backbone are necessary for efficient DNA vaccination, we studied the effect of one such ISS, the 5'-AACGTT-3' motif, in our system. Treatment with a DNA vaccine encoding myelin basic protein peptide 68-85 and containing three ISS of 5'-AACGTT-3' sequence suppressed clinical signs of EAE, while a corresponding DNA vaccine without such ISS had no effect. We further observed reduced proliferative T cell responses in rats treated with the ISS-containing DNA vaccine, compared with controls. We also studied the possible impact of coinjection of plasmid DNA encoding rat cytokines IL-4, IL-10, GM-CSF, and TNF-alpha with the ISS-containing DNA vaccine. Coinjection of IL-4-, IL-10-, or TNF-alpha-coding cDNA inhibited the suppressive effect of the DNA vaccine on EAE, whereas GM-CSF-coding cDNA had no effect. Coinjection of cytokine-coding cDNA with the ISS-deficient DNA vaccine failed to alter clinical signs of EAE, We conclude that the presence of ISS and induction ofa local T1 cytokine milieu is decisive for specific protective DNA vaccination in EAE.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/08/20 alle ore 16:59:13