Dating the origin of the ccr5 delta32
Although there are advances in the treatment of GVHD, this inflammatory immunoreaction is still responsible for 15% of treatment related mortality .Therefore, understanding and manipulating the mechanisms of GVHD is of important scientific and clinical impact.However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown.In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD.It is supposed that this deletion causes an alteration in T-cell response to inflammation.For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD) and graft rejection.
The aberrant gene product from CCR5-delta32 builds an intracellular complex with the CXCR4 receptor preventing the expression on the cell surface.
Once internalized, these receptors tend to recycle to the cell surface in time.
Most chemokines activate more than one receptor subtype and like other chemokine receptors, CCR5 can bind several chemokines .
Furthermore, the first CCR5 inhibitors have been tested concerning their therapeutic significance in terms of transplantation immunology [12, 13].
First clinical data will probably be available soon from a trial introducing the CCR5 inhibitor Maraviroc into allogeneic hematpoietic stem cell transplantation (HSCT) from the Abramson Cancer Center of the University of Pennsylvania (NIH clinical trial number: NCT00948753).
figured out a possible role for CCR5 during infection with the West Nile virus (WNV) .