Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution.
Graft-versus-host disease (GVHD), a major complication after allogeneic transplantation, can be abrogated by the Campath (anti-CD52) monoclonal antibody. The induction of acute GVHD requires host antigens to be presented to donor T cells by antigen-presenting cells (APCs). Recent evidence has suggested that only host APCs can interact with donor T cells in the induction of GVHD. Because CD52 has been reported to be expressed on DCs, we reasoned that pretransplant Campath-1G might have a direct effect on circulating DCs in addition to any effects on donor T cells. Using direct immunostaining, we demonstrated expression of CD52 on DCs and that Campath-1G killed purified DCs in vitro. In vivo Campath also depleted DCs. Twenty-four hours after the first dose of Campath-1G, circulating DCs were reduced by a mean of 79% (range, 44%-96%). By day 0 after 5 doses of Campath-1G and chemoradiotherapy conditioning, DCs became undetectable in 7 of 9 cases, whereas in 6 of 7 patients receiving conditioning therapy without Campath-1G, host DCs were still detectable. The reconstitution of circulating DCs after transplantation was not affected by Campath-1G and in both groups DC1 (CD11c(+)) recovered more rapidly than DC2 (CD11c(-)). Analysis of chimerism confirmed that the DCs recovering after transplantation in patients receiving Campath-1G were of donor origin. We conclude that in vivo Campath-1G causes a rapid depletion of host circulating DCs and that this may, in part, explain the low incidence of acute GVHD. The reconstitution of donor DCs was not delayed, which may be important in preserving immune reconstitution.
Klangsinsirikul
Phennapha
P
Division of Haematology, School of Clinical Laboratory Sciences, University of Nottingham, City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom.
Carter
G Ian
GI
Byrne
Jennifer L
JL
Hale
Geoff
G
Russell
Nigel H
NH
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D051861:Kangai-1 Protein; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D008212:Lymphocyte Depletion; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy; D008562:Membrane Glycoproteins / Q000235:genetics; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D007166:Immunosuppressive Agents; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D000074323:Alemtuzumab