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

I. S. El-Amouri, M. Bani-Ahmad, Y. Tang-Feldman, F. Lin, C. Ko, Claire Pomeroy, O. R. Oakley

Research output: Contribution to journalArticle

7 Scopus citations

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 fromneurological 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 postallo-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.

Original languageEnglish (US)
Pages (from-to)379-391
Number of pages13
JournalClinical and Experimental Immunology
Volume162
Issue number2
DOIs
StatePublished - Nov 2010

Keywords

  • CD55
  • Complement regulatory proteins
  • DAF
  • GFP-MCMV (RVG102)
  • ICAM 1
  • MCMV
  • VCAM-1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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