Role of regulatory T cells in tolerance to coagulation factors.
The immune response to coagulation factors VIII or IX, in particular formation of inhibitory antibodies, complicates treatment of hemophilia. Therefore, a number of recent studies in animal models have explored novel approaches toward induction of immune tolerance in protein or gene replacement therapy. Strong evidence has emerged that regulatory T cells (Treg) are an important component of the mechanism by which tolerance is maintained and inhibitor formation, a T help dependent response, is prevented. Limited data in patients also support this concept. In particular, CD4+ CD25+ FoxP3+ Treg, whether naturally occurring or induced, have been invoked in suppression of antibody and of cytotoxic T lymphocyte responses to the therapeutic clotting factor. This review summarizes the data on this emerging concept of Treg-mediated regulation of the immune response in treatment of hemophilia, strategies and mechanisms of Treg induction and function, and the implications for development of immune tolerance protocols.
Cao
O
O
Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.
Loduca
P A
PA
Herzog
R W
RW
D001779:Blood Coagulation Factors / Q000276:immunology*; D006467:Hemophilia A / Q000276:immunology / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D001779:Blood Coagulation Factors