2003; baxter - Supplements - Haematologica

68J.M.R. Saint-Remyone being to decide which epitope to use. As statedabove, the size of the T cell repertoire is suchthat a T cell can be found to any possible epitope.However, only major epitopes have to be hit, anddefining which epitope is a major one is not aneasy task. Peptides have a short half-life, so waysto increase their resistance to proteolytic enzymesand/or prolong their half-life will have to befound. Such peptides also offer the possibility toproduce variants with which it is possible tomodulate the affinity of MHC class II determinants.A special case should be made concerning regulatoryT cells, and specifically a recently identifiedsubpopulation of CD4 + T cells carrying theCD25 (IL-2) receptor, and which are activelyselected in the thymus. Such CD4 + CD25 + T cellsexert their regulatory properties by a combinationof mechanisms including secretion of suppressivecytokines such as IL-10 and TGF-β andcell-to-cell contact. It is too early to decidewhether such regulatory T cells will be useful ineliminating FVIII inhibitors, but we can alreadyanticipate a number of studies in this direction.Perhaps the ultimate goal in the therapy ofFVIII inhibitors would be to eliminate FVIII-specificimmunocompetent cells. Actual deletion ofB and T cells occurs as part of the homeostasis ofthe immune system. Deletion occurs as a resultof either neglect or overstimulation. An immuneresponse is triggered only whenever there is asubtle equilibrium between activation and suppressionsignals. If activation goes too far, thenspecific B as well as T cells are eliminated. Thebest example of this is the so-called activationinducedcell death, which drives T cells into committingsuicide via the overexpression of FAS andFas-ligand. It is however too early to decidewhether it would be possible to master such aphenomenon for therapeutic purposes. One mayperhaps argue that treating patients withinhibitor by infusing large doses of FVIII alreadyrepresents an example of specific T cell deletion.Experiments are ongoing to determine whetherthis is the case.This short overview of the prospects forimmune therapy of FVIII inhibitors should leavethe reader with the strong feeling that many possibilitiesexist, which, within the forthcoming tenyears, should be reducible to practice.haematologica vol. 88(supplement n. 12):september 2003