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Article
Nature Medicine  10, 510 - 517 (2004)
Published online: 18 April 2004; | doi:10.1038/nm1038


There is an Erratum (June 2004) associated with this Article.

Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease

Miriam Merad1, 6, Petra Hoffmann2, 6, Erik Ranheim1, Sarah Slaymaker3, Markus G Manz1, 6, Sergio A Lira4, Israel Charo3, Donald N Cook5, Irving L Weissman1, Samuel Strober2 & Edgar G Engleman1

1  Department of Pathology, Stanford University School of Medicine Palo Alto, California 94304, USA.

2  Department of Medicine, Stanford University School of Medicine Palo Alto, California 94304, USA.

3  Cardiovascular Research Institute and the Department of Medicine, University of California, San Francisco, California 94104, USA.

4  Department of Immunobiology, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.

5  Division of Pulmonary and Critical Care, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

6  Present addresses: Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mt. Sinai School of Medicine, New York, New York 10029, USA (M.M.); Department of Medicine, University of Regensburg, D-93053 Germany (P.H.); and Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland (M.G.M.).

Correspondence should be addressed to Miriam Merad miriam.merad@mssm.edu
Skin is the most commonly affected organ in graft-versus-host disease (GVHD). To explore the role of Langerhans cells in GVHD, the principal dendritic cells of the skin, we studied the fate of these cells in mice transplanted with allogeneic bone marrow. In contrast to other dendritic cells, host Langerhans cells were replaced by donor Langerhans cells only when donor T cells were administered along with bone marrow, and the extent of Langerhans cell chimerism correlated with the dose of donor T cells injected. Donor T cells depleted host Langerhans cells through a Fas-dependent pathway and induced the production in skin of CCL20, which was required for the recruitment of donor Langerhans cells. Administration of donor T cells to bone marrow−chimeric mice with persistent host Langerhans cells, but not to mice whose Langerhans cells had been replaced, resulted in marked skin GVHD. These findings indicate a crucial role for donor T cells in host Langerhans cell replacement, and show that host dendritic cells can persist in nonlymphoid tissue for the duration of an animal's life and can trigger GVHD despite complete blood chimerism.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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