Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice

Wikstrom, Matthew E., Fleming, Peter, Kuns, Rachel D., Schuster, Iona S., Voigt, Valentina, Miller, Gregory, Clouston, Andrew D., Tey, Siok-Keen, Andoniou, Christopher E., Hill, Geoffrey R. and Degli-Esposti, Mariapia A. (2015) Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice. Blood, 126 12: 1503-1514. doi:10.1182/blood-2015-01-622837


Author Wikstrom, Matthew E.
Fleming, Peter
Kuns, Rachel D.
Schuster, Iona S.
Voigt, Valentina
Miller, Gregory
Clouston, Andrew D.
Tey, Siok-Keen
Andoniou, Christopher E.
Hill, Geoffrey R.
Degli-Esposti, Mariapia A.
Title Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
0006-4971
Publication date 2015-09-17
Sub-type Article (original research)
DOI 10.1182/blood-2015-01-622837
Open Access Status Not Open Access
Volume 126
Issue 12
Start page 1503
End page 1514
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2016
Language eng
Formatted abstract
Viral infection is a common, life-threatening complication after allogeneic bone marrow transplantation (BMT), particularly in the presence of graft-versus-host disease (GVHD). Using cytomegalovirus (CMV) as the prototypic pathogen, we have delineated the mechanisms responsible for the inability to mount protective antiviral responses in this setting. Although CMV infection was self-limiting after syngeneic BMT, in the presence of GVHD after allogeneic BMT, CMV induced a striking cytopathy resulting in universal mortality in conjunction with a fulminant necrotizing hepatitis. Critically, GVHD induced a profound dendritic cell (DC) defect that led to a failure in the generation of CMV-specific CD8+ T-cell responses. This was accompanied by a defect in antiviral CD8+ T cells. In combination, these defects dramatically limited antiviral T-cell responses. The transfer of virus-specific cells circumvented the DC defects and provided protective immunity, despite concurrent GVHD. These data demonstrate the importance of avoiding GVHD when reconstructing antiviral immunity after BMT, and highlight the mechanisms by which the adoptive transfer of virus-specific T cells overcome the endogenous defects in priming invoked by GVHD.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
 
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