Hemophilia factor VIII therapy. B- and T-cell tolerance: from basic concepts to clinical practice

Recent advances in the understanding of the mechanisms by which tolerance develops in both B- and T- cells have led to a re-appraisal of possible methods which could be applicable in clinical settings such as hemophilia patients with inhibitors. Thus, it is now clear that a number of mechanisms operate in such a way as to actively induce anergy of B- or T- cells, or even to specifically delete cells in the periphery. The characteristics inherent to the B- and T- cell repertoires and peripheral pools play a major role in the efficiency and maintenance of tolerance induction. The purpose of this manuscript is to review the mechanisms of tolerance induction briefly so as to provide a framework for the understanding of current and future attempts to achieve Factor VIII unresponsiveness in hemophilia A patients.