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. IntroductionHigh-dose chemoradiotherapy followed by the allogeneic transplantation of hematopoietic stem cells from either bone marrow (BM) or peripheral blood stem cells (PBSCs) is widely used in the treatment of malignant and nonmalignant hematologic diseases. However, allogeneic transplantation is frequently associated with the development of acute graft-versus-host disease (GVHD), which is thought to occur as a result of donor T-cell activation damaging host tissues particularly affecting the liver, skin, and gastrointestinal tract. 1,2 Current therapeutic approaches to the prevention of acute GVHD after transplantation include immunosuppression with agents such as cyclosporin and methotrexate. However, despite these measures GVHD still remains a significant cause of morbidity and mortality. [3][4][5] Alternative strategies for the prevention of acute GVHD have focused on the depletion of donor T cells from the graft before infusion into the host. [6][7][8] Although it has been recognized for many years that T-cell depletion decreases the risk of GVHD development, 6,9 it also increases the risk of leukemia relapse in chronic myeloid leukemia 10 and graft rejection. 11 A number of different approaches to T-cell depletion have been used including CD34 ϩ cell selection 12,13 and ex vivo treatment of the graft with monoclonal antibodies. For this purpose, Campath-1M, which recognizes the CD52 antigen, has been...

Many studies suggest that increased proteolysis accounts for the epithelial basement membrane (EBM) breaks commonly seen in carcinomas. As failure to produce or maintain EBM may also be important, we chose to investigate synthesis of basement membrane collagen-IV in human colorectal carcinomas. First, to determine the cellular origin of EBM collagen-IV, species-specific antibodies were used to analyse caecal xenografts of 4 different human colorectal-carcinoma-derived cell lines. The results of this study suggest an exclusively stromal cell origin for EBM collagen-IV. Next, the distribution of periglandular myofibroblasts in carcinomas was examined, since in normal mucosa their location and ultrastructural features suggest that they play a role in EBM maintenance. They were generally abundant in normal mucosa and adenomas, but sparsely distributed in carcinomas, particularly at the invasive periphery where EBM collagen-IV immunostaining is most deficient. Finally, the in situ hybridization technique was used to define cell populations synthesizing collagen-IV. In normal mucosa, no collagen-IV mRNA was detected in any component, while in carcinomas, the mRNA was clearly detectable in vascular endothelial cells but not in any other cell type. Increased vascular collagen-IV production in carcinomas may be at least partly due to tumour-induced angiogenesis, since new blood-vessel formation requires the synthesis of new vascular basement membranes.