ANIMAL MODEL FOR VIRAL INDUCED BMT COMPLICATIONS

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from the Investigator's abstract): The studies
proposed in this application will generate a new experimental mouse model
for the investigation of questions concerning the clinical association of
cytomegalovirus (CMV) and graft-versus-host disease (GVHD). Mice will be
infected with murine cytomegalovirus (MCMV) and monitored until infectious
virus is no longer detectable (chronically infected). These animals will
subsequently receive an allogeneic bone marrow transplant. The major
objective of the study is to investigate how donor T-cells effect the
outcome of an allogeneic bone marrow transplant in recipients previously
infected target tissues including the lung. Virus expression will be
assessed by cellular (plaque) and molecular (PCR) assay and examined with
respect to donor effector function. Clinical signs and histopathology of
GVHD and MCMV target issues will be assessed to correlate the presence and
levels of virus with the pathogenesis occurring following allogeneic BMT.
In tissues where viral expression precedes or coincides with cellular
infiltrates, CD3+ T-cells will be isolated and characterized by phenotype to
identify the infiltrating populations and compare to populations identified
in non-infected recipients. The infiltrates will be assessed functionally
for anti-host and anti-viral reactivity. To address how donor cells can
affect virus expression following transplant, functionally defective T-cells
for the production of interferon-gamma and mediation of cytotoxicity via
perforin and/or FasL will be transplanted. Finally, bone marrow transplants
utilizing donor T-cells specific for non-self ('host') MHC plus MCMV will be
performed to test the hypothesis that such cells can control MCMV infection
and diminish GVHD post-transplant.
StatusFinished
Effective start/end date12/1/933/31/03

Funding

  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute: $213,627.00
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute: $220,037.00
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute

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