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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-04-1093. This Article Full Text (PDF) Erratum (v105,p3018) All Versions of this Article: 2002-04-1093v1 101/4/1422    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ratzinger, G. Articles by Young, J. W Search for Related Content PubMed PubMed Citation Articles by Ratzinger, G. Articles by Young, J. W Social Bookmarking                   What's this? Submitted April 10, 2002 Accepted September 6, 2002 Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab (Campath-1H) activity at the level of antigen-presentation in allogeneic graft-host interactions in transplantation Gudrun Ratzinger, John L Reagan, Glenn Heller, Klaus J Busam, and James W Young* Laboratory of Cellular Immunobiology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Surgical Pathology Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Allogeneic Transplantation and Clinical Immunology Services, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Weill Medical College of Cornell University, New York, NY, USA * Corresponding author; email: youngjw{at}mskcc.org. Anti-CD52 depletes both host and donor T cells when used in preparative regimens for allogeneic transplantation. This promotes engraftment even after nonmyeloablative conditioning and limits graft-vs-host disease (GvHD) even after unrelated and/or MHC disparate allografts. We asked whether anti-CD52 differentially targets antigen-presenting cells (APCs), in addition to depleting T cells. Monocyte-derived dendritic cells (moDCs) expressed abundant CD52 as expected. Langerhans cells (LCs) and dermal-interstitial DCs (DDC-IDCs), however, never expressed CD52. Immunostaining of skin and gut confirmed the absence of CD52 on these resident DC populations under both steady state and inflammatory conditions. Although anti-CD52 functions primarily by antibody dependent cellular cytotoxicity (ADCC) in vivo, assessment of its activity in vitro included complement-dependent lysis of CD52+ cells. Anti-CD52 did not impair DC-T cell adhesion, diminish DC-stimulated T-cell proliferation, or alter moDC development in vitro. We propose that anti-CD52 abrogates GvHD not only by T cell-depletion, but also by removing moDCs and their precursors. This would mitigate moDC phagocytosis and presentation of host-derived Ags to donor T cells in the inflammatory peri-transplant environment, thereby limiting GvHD. The sparing of LCs and DDC-IDCs by anti-CD52, as well as the recovery of donor-derived moDCs in a less inflammatory environment later post-transplant, may allow all these DCs to exert formative roles in graft versus tumor (GvT) reactions and immune reconstitution. Whether these results support a separation of deleterious from beneficial graft-host interactions at the level of antigen-presentation, rather than solely at the level of T cells, will require evaluation in animal models. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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