Kurzfassung

Allogeneic hematopoietic stem-cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody Alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair post-transplant antiviral and antitumor immunity. Among viral infections after Alemtuzumab-based allo-SCT, those with herpes viruses including cytomegalovirus and varicella-zoster virus (VZV) play a dominant role. These infections cause...Allogeneic hematopoietic stem-cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody Alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair post-transplant antiviral and antitumor immunity. Among viral infections after Alemtuzumab-based allo-SCT, those with herpes viruses including cytomegalovirus and varicella-zoster virus (VZV) play a dominant role. These infections cause considerable morbidity and – in case of organ involvement – also significant mortality.
As the immune surveillance against herpes viruses is mainly mediated by virus-reactive T cells, the assessment of absolute T cell numbers after transplantation is generally used to determine the risk for herpes virus reactivation and the duration of prophylaxis with antiviral medication. However, normal T cell counts do not necessarily provide effective antiviral immunity, as we have recently observed in patients with visceral VZV infection after Alemtuzumab-based allo-SCT.
In vitro assays measuring the frequency of virus-specific T cells in peripheral blood are more informative, but require the knowledge of viral peptide epitopes and HLA restriction elements. While the latter are already well-known for cytomegalovirus, VZV is poorly characterized with regard to T cell epitopes and restricting HLA molecules. Therefore, this project proposal aims at the set-up of an easy-to-use in vitro assay allowing the determination and monitoring of the frequency of VZV-specific T cells in peripheral blood mononuclear cells. To establish such an assay, we will apply our extensive methodological experience in the sensitive detection and detailed characterization of antigen-specific T cells in vitro. The ultimate goal of this project is to use the frequency of VZV-specific T cells in peripheral blood as a surrogate marker in patients undergoing treatment with Alemtuzumab (or other T-cell depleting agents) to better define their individual risk for VZV reactivation as well as their need for taking antiviral prophylactic medication.» weiterlesen» einklappen