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Direct suppression of autoaggressive CD8+ T cells with CD80/86 blockade in CD8+ T cell-mediated polymyositis models of mice
H. Hasegawa1, K. Kawahata2, F. Mizoguchi3, N. Okiyama4, N. Miyasaka5, H. Kohsaka6
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. kohsaka.rheu@tmd.ac.jp
CER10019
2017 Vol.35, N°4
PI 0593, PF 0597
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PMID: 28134083 [PubMed]
Received: 17/10/2016
Accepted : 14/12/2016
In Press: 27/01/2017
Published: 13/07/2017
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.
