Direct suppression of autoaggressive CD8+ T cells with CD80/86 blockade in CD8+ T cell-mediated polymyositis models of mice.
Clin Exp Rheumatol
; 35(4): 593-597, 2017.
Article
em En
| MEDLINE
| ID: mdl-28134083
ABSTRACT
OBJECTIVES:
CD80/86 blockade to inhibit CD28 costimulation suppressed alloreactive human and murine CD4+ T cells but not alloreactive CD8+ T cells. In contrast, CD28 costimulation augments CD8+ T cell-mediated cell lysis in antigen-nonspecific stimulation. The present study was conducted to discern whether the CD80/86 blockade exerts therapeutic effects on CD8+ T cell-mediated polymyositis (PM) models of mice and whether the effects could be attributable to direct suppression of autoantigen-specific CD8+ T cells.METHODS:
C protein-induced myositis (CIM) was induced in mice with intradermal injection of C protein fragments. C protein peptide-induced myositis (CPIM), in which autoaggressive CD8+ T cells are activated without CD4+ T cell help, was induced in mice with intravenous injection of dendritic cells (DCs) loaded with CD8+ T cell-epitope peptides derived from the C protein fragment. The immunised mice were treated with CTLA4-Ig or anti-CD80 and anti-CD86 antibodies (anti-CD80/86 Abs). The muscles were evaluated histologically 21 days after the C protein immunisation or 7 days after the DC injection.RESULTS:
CIM was suppressed in the mice treated with CTLA4-Ig or anti-CD80/86 Abs administered prophylactically from the day of immunisation and therapeutically after the disease onset. CPIM was suppressed when CTLA4-Ig was administered concurrently with the DC injection.CONCLUSIONS:
The CD80/86 blockade was effective in PM models of mice. Amelioration of CPIM indicates direct suppression of CD8+ T cells by the CD80/86 blockade. CTLA4-Ig should be a potential therapeutic agent of PM and other CD8+T cell-mediated diseases by suppressing both autoantigen-specific CD4+ and CD8+ T cells.
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Base de dados:
MEDLINE
Assunto principal:
Polimiosite
/
Músculo Esquelético
/
Linfócitos T CD8-Positivos
/
Abatacepte
/
Anticorpos
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article