Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease.
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.
Wilson
John
J
Mater Medical Research Institute, South Brisbane, Queensland 4101, Australia.
Cullup
Hannah
H
Lourie
Rohan
R
Sheng
Yonghua
Y
Palkova
Anna
A
Radford
Kristen J
KJ
Dickinson
Anne M
AM
Rice
Alison M
AM
Hart
Derek N J
DN
Munster
David J
DJ
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097802:CD83 Antigen
D000906:Antibodies; D015703:Antigens, CD; D016207:Cytokines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen