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

Abstract

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 × 10⁵ 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)-γ production by lung CD8 T cells, and infection with MCMV further exacerbated both intracellular IFN-γ 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.

• Authors: I S El-Amouri, M Bani-Ahmad, Y Tang-Feldman, F Lin, C Ko, C Pomeroy, O R Oakley
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 162 Issue 2 Pg. 379-91 (Nov 2010) ISSN: 1365-2249 [Electronic] England
• PMID: 20840652 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2010 The Authors; Clinical and Experimental Immunology © 2010 British Society for Immunology.

Chemical References

• CD55 Antigens
• Immediate-Early Proteins
• Vascular Cell Adhesion Molecule-1
• complement C3a, des-Arg-(77)-
• Intercellular Adhesion Molecule-1
• Complement C3a
• Complement C3d
• Interferon-gamma

Topics

• Animals
• Body Weight (immunology)
• Bone Marrow Transplantation (immunology, mortality, pathology)
• CD4-Positive T-Lymphocytes (pathology)
• CD55 Antigens (genetics, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Cell Count
• Complement Activation (immunology)
• Complement C3a (metabolism)
• Complement C3d (metabolism)
• Cytomegalovirus Infections (immunology, metabolism)
• Female
• Immediate-Early Proteins (immunology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interferon-gamma (metabolism)
• Lung (metabolism, pathology, virology)
• Lymphocyte Activation (genetics, immunology)
• Lymphocytes (immunology, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Survival Analysis
• Transplantation, Homologous
• Vascular Cell Adhesion Molecule-1 (metabolism)