In vitro depletion of tissue-derived dendritic cells by CMRF-44 antibody and alemtuzumab: implications for the control of Graft-versus-host disease.
Graft-versus-host disease (GvHD), a life-threatening complication of bone marrow transplantation, is initiated by donor T cells reacting to recipient dendritic cells (DC). GvHD can be controlled by attenuating donor T cells, but few strategies exist to target DC, particularly resident tissue DC, despite recent evidence of their importance. In this report, CMRF-44, a mouse monoclonal IgM reactive to human DC, is tested against human Langerhans cells (LC) in vitro. CMRF-44 antigen is expressed at low level on fresh LC but is up-regulated 40-60-fold during migration. CMRF-44 and complement kill more than 97% of migratory LC in vitro and inhibit allostimulation by LC up to 95%. In comparison, alemtuzumab, which binds CD52, reacts weakly with primary LC and fails to induce significant lysis with complement (less than 5%). These results highlight the potential of new therapeutic antibodies active against tissue DC to control graft-versus-host reactions.
Collin
Matthew P
MP
Hematological Sciences, University of Newcastle, Newcastle-upon-Tyne, NE2 4HH, UK. matthew.collin@ncl.ac.uk
Munster
David
D
Clark
Georgina
G
Wang
Xiao-Nong
XN
Dickinson
Anne M
AM
Hart
Derek N
DN
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology; D002465:Cell Movement; D003165:Complement System Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology* / Q000494:pharmacology*; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000941:Antigens; D007075:Immunoglobulin M; D000074323:Alemtuzumab; D003165:Complement System Proteins