Differential CD52 expression by distinct myeloid dendritic cell subsets: Implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation Journal Article
| Authors: | Ratzinger, G.; Reagan, J. L.; Heller, G.; Busam, K. J.; Young, J. W. |
| Article Title: | Differential CD52 expression by distinct myeloid dendritic cell subsets: Implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation |
| Abstract: | Alemtuzumab (anti-CD52; Campath 1-H) 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-versus-host disease (GVHD) even after unrelated or major histocompatibility complex (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 antigens to donor T cells in the inflammatory peritransplantation 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 after transplantation, 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 further evaluation. © 2003 by The American Society of Hematology. |
| Keywords: | immunohistochemistry; controlled study; allograft; transplantation, homologous; human cell; drug activity; rituximab; antigen expression; t lymphocyte; t-lymphocytes; cell division; steady state; dendritic cell; inflammation; allogenic bone marrow transplantation; cytotoxicity; in vitro study; cell population; antigen presentation; dendritic cells; lymphocyte culture test, mixed; antibodies, monoclonal; antigen; antigens, neoplasm; guanine; graft versus host reaction; antiinflammatory activity; bone marrow cell; antigens, cd; monocyte; phagocytosis; major histocompatibility complex; graft vs host disease; cell adhesion; glycoproteins; antibodies, neoplasm; intestines; lymphocyte depletion; alemtuzumab; normal human; cd52 antigen; coculture techniques; langerhans cell; granulocytes; graft vs host reaction; antibody-dependent cell cytotoxicity; humans; human; priority journal; article |
| Journal Title: | Blood |
| Volume: | 101 |
| Issue: | 4 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2003-02-15 |
| Start Page: | 1422 |
| End Page: | 1429 |
| Language: | English |
| DOI: | 10.1182/blood-2002-04-1093 |
| PUBMED: | 12393688 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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