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In Vitro Depletion of Tissue-Derived Dendritic Cells by CMRF-44 Antibody and Alemtuzumab: Implications for the Control of Graft-Versus-Host Disease

2005; Wolters Kluwer; Volume: 79; Issue: 6 Linguagem: Inglês

10.1097/01.tp.0000149321.86104.c4

1534-6080

Matthew Collin, David J. Munster, Georgina J. Clark, Xiaonong Wang, Anne M. Dickinson, Derek N.J. Hart,

Hematopoietic Stem Cell Transplantation

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.