Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells.
Proc Natl Acad Sci U S A
; 107(40): 17280-5, 2010 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-20855626
ABSTRACT
In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity appear to be particularly promising targets for antigen-specific induction of tolerance without compromising desired protective host immune responses. Several lines of evidence suggest that delivery of antigens to antigen-presenting dendritic cells (DCs) in the steady state (i.e., to immature DCs) may represent a suitable approach to induce antigen-specific T-cell tolerance peripherally. Here, we report that anti-DEC205-mediated delivery of the self-peptide proteolipid protein (PLP)139-151 to DCs ameliorated clinical symptoms in the PLP-induced SJL model of experimental autoimmune encephalomyelitis. Splenocytes from treated mice were anergized to PLP139-151, and IL-17 secretion was markedly reduced. Moreover, we show directly, using transgenic CD4(+) Vß6(+) TCR T cells specific for PLP139-151, that, under the conditions of the present experiments, these cells also became anergic. In addition, evidence for a CD4(+) T cell-mediated suppressor mechanism was obtained.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Células Dendríticas
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Proteína Proteolipídica de Mielina
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Encefalomielite Autoimune Experimental
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Tolerância Imunológica
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos