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Updated: Jun 8, 2026
Bone Marrow Transplantation Platform to Investigate the Role of Dendritic Cells in Graft-versus-Host Disease
Published on: March 17, 2020
Increased morbidity and mortality in murine cytomegalovirus-infected mice following allogeneic bone marrow transplant
I S El-Amouri1, M Bani-Ahmad, Y Tang-Feldman
1Center of Excellence in Reproductive Sciences, University of Kentucky, Lexington, 40536-0084, USA.
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.
Insights
Cytomegalovirus (CMV) infection increases mortality after bone marrow transplants. This study shows CMV reduces decay accelerating factor (DAF), worsening transplant outcomes and increasing T cell responses.
Area of Science:
- Immunology
- Transplantation immunology
- Virology
Background:
- Cytomegalovirus (CMV) infection is a major cause of complications and death after allogeneic bone marrow transplantation (allo-BMT).
- The precise mechanisms linking CMV infection to increased morbidity and mortality post-allo-BMT are not fully understood.
- While T cell responses are key, complement activation's role in graft-versus-host disease (GVHD) is increasingly recognized.
Purpose of the Study:
- To investigate the impact of murine cytomegalovirus (MCMV) infection on decay accelerating factor (DAF) expression.
- To elucidate MCMV's role in exacerbating morbidity and mortality following allo-BMT.
Main Methods:
- Mice were infected with a sublethal dose of MCMV.
- DAF expression was assessed on lung tissues and lymphocytes post-MCMV infection and allo-BMT.
- Mortality rates and intracellular interferon-gamma (IFN-γ) production by CD8 T cells were analyzed in DAF knock-out and wild-type mice.
Main Results:
- MCMV infection led to reduced DAF expression on lung tissues and lymphocytes post-allo-BMT.
- Recipient DAF knock-out mice exhibited increased mortality post-allo-BMT, mirroring MCMV-infected wild-type recipients.
- DAF knock-out mice showed elevated intracellular IFN-γ production by lung CD8 T cells, which was further amplified by MCMV infection, alongside increased mortality.
Conclusions:
- MCMV infection exacerbates morbidity and mortality post-allo-BMT.
- Reduced surface DAF expression is a key mechanism by which MCMV infection augments negative outcomes after allo-BMT.
- Targeting DAF may offer a therapeutic strategy to mitigate CMV-related complications in allo-BMT recipients.
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