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Open Access Publications from the University of California

Effect of Cytotoxic T-Lymphocyte-Associated Protein 4 Immunoglobulin (CTLA-4Ig) Fusion Protein on Recruitment of Regulatory T Cells and Macrophages to Dystrophic Muscles in mdx Mouse Model of Duchenne Muscular Dystrophy

  • Author(s): Kok, Su-yin
  • Advisor(s): Tidball, James G
  • et al.

Duchenne muscular dystrophy (DMD) is a fatal X-linked disease characterized by chronic muscle degeneration. Because the immune system modulates the severity of DMD, it provides a potential therapeutic target for DMD. Previous investigations have shown that cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA-4Ig) fusion protein inhibits T cell activation and reduces migration of macrophages. The objective of this study was to assess CTLA-4Ig as a potential DMD immunotherapy. Mdx mice, a mouse model of DMD, were administered CTLA-4Ig and euthanized at 4-week or 3-months old. At the peak of muscle inflammation, CTLA-4Ig-treated 4-week mice exhibited significantly reduced necrosis and reduced numbers of CD68+ M1 macrophages and CD163+ M2 macrophages in muscle and in individual injured myofibers. At 3-months, we saw little treatment effects indicating that the influence of CTLA-4Ig is transient. Due to the reduction in necrosis and inflammatory cells in the dystrophic muscles, CTLA-4Ig is a promising immunotherapy for DMD.

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