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Rockefeller University Press, Journal of Experimental Medicine, 5(206), p. 1203-1203, 2009

DOI: 10.1084/jem.20070723041509c

Rockefeller University Press, Journal of Experimental Medicine, 2(206), p. 387-398, 2009

DOI: 10.1084/jem.20070723

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

Journal article published in 2009 by John Wilson, Hannah Cullup, Rohan Lourie, Yonghua Sheng ORCID, Anna Palkova, Kristen J. Radford ORCID, Anne M. Dickinson, Alison M. Rice, Derek N. J. Hart, David J. Munster
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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 (51)Cr-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.