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¹ Mater Medical Research Institute, South Brisbane, Queensland 4101, Australia
² Haematological Sciences, Newcastle University, Newcastle-upon-Tyne NE2 4HH, England, UK
³ Mater Health Services Pathology, South Brisbane, Queensland 4101, Australia

CORRESPONDENCE David J. Munster: dmunster{at}mmri.mater.org.au OR Derek N.J. Hart: dhart{at}mmri.mater.org.au

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.

Abbreviations used: ADCC, antibody-dependent cellular cytotoxic; allo, allogeneic; ATG, anti-thymocyte globulin; FMP, influenza matrix protein; GVHD, acute graft-versus-host disease; GVL, graft versus leukemia; HSCT, hematopoietic stem cell transplantation; MoDC, monocyte-derived DC.

© 2009 Wilson et al.
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