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Publication : Increased morbidity and mortality in murine cytomegalovirus-infected mice following allogeneic bone marrow transplant is associated with reduced surface decay accelerating factor expression.

First Author  El-Amouri IS Year  2010
Journal  Clin Exp Immunol Volume  162
Issue  2 Pages  379-91
PubMed ID  20840652 Mgi Jnum  J:174160
Mgi Id  MGI:5052008 Doi  10.1111/j.1365-2249.2010.04241.x
Citation  El-Amouri IS, et al. (2010) Increased morbidity and mortality in murine cytomegalovirus-infected mice following allogeneic bone marrow transplant is associated with reduced surface decay accelerating factor expression. Clin Exp Immunol 162(2):379-91
abstractText  Infection with cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following allogeneic bone marrow transplantation (allo-BMT). The manifestations of CMV infection can range from neurological and haematological abnormalities to diminished graft survival and, in extreme cases, death. Many clinical studies have shown a direct correlation between cytomegalovirus infection and increased morbidity and mortality post allo-BMT, yet the exact mechanism is not well understood. Although driven primarily by T cell responses, the role of complement activation in acute and chronic graft-versus-host disease (GVHD) has also become more evident in recent years. The present studies were performed to examine the effects of murine cytomegalovirus (MCMV) infection on decay accelerating factor (DAF) and MCMVs role in exacerbating morbidity and mortality post-allo-BMT. Mice infected previously with a sublethal dose of MCMV (1 x 10 plaque-forming units) have reduced expression of DAF on lung tissues and lymphocytes following allo-BMT. More importantly, mortality rates post-allo-BMT in recipient DAF knock-out mice receiving wild-type bone marrow are increased, similar to wild-type MCMV-infected recipient mice. Similarly, DAF knock-out mice showed greater intracellular interferon (IFN)-gamma production by lung CD8 T cells, and infection with MCMV further exacerbated both intracellular IFN-gamma production by CD8 T cells and mortality rates post-allo-BMT. Together, these data support the hypothesis that MCMV infection augments morbidity and mortality post-allo-BMT by reducing surface DAF expression.
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