Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice.
J Clin Invest
; 104(5): 599-610, 1999 Sep.
Article
em En
| MEDLINE
| ID: mdl-10487774
ABSTRACT
The mechanisms underlying the initiation of virus-induced autoimmune disease are not well understood. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a mouse model of multiple sclerosis, is initiated by TMEV-specific CD4(+) T cells targeting virally infected central nervous system-resident (CNS-resident) antigen-presenting cells (APCs), leading to chronic activation of myelin epitope-specific CD4(+) T cells via epitope spreading. Here we show that F4/80(+), I-A(s+), CD45(+) macrophages/microglia isolated from the CNS of TMEV-infected SJL mice have the ability to endogenously process and present virus epitopes at both acute and chronic stages of the disease. Relevant to the initiation of virus-induced autoimmune disease, only CNS APCs isolated from TMEV-infected mice with preexisting myelin damage, not those isolated from naive mice or mice with acute disease, were able to endogenously present a variety of proteolipid protein epitopes to specific Th1 lines. These results offer a mechanism by which localized virus-induced, T cell-mediated inflammatory myelin destruction leads to the recruitment/activation of CNS-resident APCs that can process and present endogenous self epitopes to autoantigen-specific T cells, and thus provide a mechanistic basis by which epitope spreading occurs.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Sistema Nervoso Central
/
Doenças Desmielinizantes
/
Theilovirus
/
Infecções por Cardiovirus
/
Apresentação de Antígeno
/
Proteína Proteolipídica de Mielina
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Modelos Animais de Doenças
/
Esclerose Múltipla
/
Epitopos
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos