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Research Update: T Cells are Key Players in Immune System Tolerance of Clotting Factor

Researchers from the University of Florida (UF) in Gainesville recently reviewed data that provide convincing evidence that regulatory T cells, called Treg, play a vital role in the prevention of inhibitor antibodies to clotting factors. Treg are a special type of T cell that suppresses activation of the immune system. The findings could have positive implications for both factor replacement therapy and potential gene therapies for hemophilia. The lead author of the study was Ou Cao, MD, PhD, Assistant Professor, Division of Cellular and Molecular Therapy at UF.

Inhibitors are a major complication in the clinical management of hemophilia. They are costly and difficult to treat. Approximately 10% to 30% of hemophilia A patients and 1%-4% of hemophilia B patients develop inhibitors, which occur when the body’s immune system recognizes infused clotting factor as a foreign substance and releases antibodies in response. These antibodies attack the factor, neutralizing its therapeutic effects.

Cao and colleagues explained that Treg are an important part of the mechanism by which inhibitor formation can be prevented and tolerance to clotting factor could be ensured. Investigators looked at CD4+ CD25+ FoxP3+ Treg specifically, concluding that whether naturally occurring or induced, these cells are “invoked” in the suppression of antibody responses to clotting factor. Treg is therefore crucial to tolerance, according to the authors.

While the risk of inhibitors with genetically triggered factor production is not fully understood, investigators believe Treg could apply to gene-based therapies as well, adding that the cells could become a key component in establishing tolerance to clotting factors in “gene- or protein-based therapies.” Cao and fellow authors conclude that novel therapies and immune tolerance induction protocols could be developed with this insight into the workings of immune regulation.

Source: Cao O, Loduca P, Herzog R. Role of Regulatory T Cells in Tolerance to Coagulation Factors. Journal of Thrombosis and Haemostasis 2009; 7 (Suppl. 1): 88-91.


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