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Lookup NU author(s): Dr Hannah Cullup, Professor Anne Dickinson
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.
Author(s): Wilson J, Cullup H, Lourie R, Sheng Y, Palkova A, Radford KJ, Dickinson AM, Rice AM, Hart DNJ, Munster DJ
Publication type: Article
Publication status: Published
Journal: The Journal of Experimental Medicine
Year: 2009
Volume: 206
Issue: 2
Pages: 387-398
Date deposited: 13/05/2010
ISSN (print): 0022-1007
ISSN (electronic): 1540-9538
Publisher: Wiley-Blackwell Publishing, Inc.
URL: http://dx.doi.org/10.1084/jem.20070723
DOI: 10.1084/jem.20070723
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