Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease

Wilson, John, Cullup, Hannah, Lourie, Rohan, Sheng, Yonghua, Palkova, Anna, Radford, Kristen J., Dickinson, Anne M., Rice, Alison M., Hart, Derek N. J. and Munster, David J. (2009) Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease. Journal of Experimental Medicine, 206 2: 387-398. doi:10.1084/jem.20070723

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Author Wilson, John
Cullup, Hannah
Lourie, Rohan
Sheng, Yonghua
Palkova, Anna
Radford, Kristen J.
Dickinson, Anne M.
Rice, Alison M.
Hart, Derek N. J.
Munster, David J.
Title Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
1540-9538
Publication date 2009-02-01
Sub-type Article (original research)
DOI 10.1084/jem.20070723
Open Access Status File (Publisher version)
Volume 206
Issue 2
Start page 387
End page 398
Total pages 12
Place of publication New York United States
Publisher Rockefeller University Press
Language eng
Subject 2403 Immunology
2723 Immunology and Allergy
2700 Medicine
Formatted abstract
Allogeneic (allo) hematopoietic stem cell transplantation is an effective therapy for hematological malignancies but it is limited by acute graft-versus-host disease (GVHD). Dendritic cells (DC) play a major role in the allo T cell stimulation causing GVHD. Current immunosuppressive measures to control GVHD target T cells but compromise posttransplant immunity in the patient, particularly to cytomegalovirus (CMV) and residual malignant cells. We showed that treatment of allo mixed lymphocyte cultures with activated human DC-depleting CD83 antibody suppressed alloproliferation but preserved T cell numbers, including those specific for CMV. We also tested CD83 antibody in the human T cell–dependent peripheral blood mononuclear cell transplanted SCID (hu-SCID) mouse model of GVHD. We showed that this model requires human DC and that CD83 antibody treatment prevented GVHD but, unlike conventional immunosuppressants, did not prevent engraftment of human T cells, including cytotoxic T lymphocytes (CTL) responsive to viruses and malignant cells. Immunization of CD83 antibody-treated hu-SCID mice with irradiated human leukemic cell lines induced allo antileukemic CTL effectors in vivo that lysed 51Cr-labeled leukemic target cells in vitro without further stimulation. Antibodies that target activated DC are a promising new therapeutic approach to the control of GVHD.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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