{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:58:03Z","timestamp":1791115083287,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Epidermal Langerhans cells (LC) are potent APCs surveying the skin. They are crucial regulators of T cell activation in the context of inflammatory skin disease and graft-versus-host disease (GVHD). In contrast to other dendritic cell subtypes, murine LC are able to reconstitute after local depletion without the need of peripheral blood-derived precursors. In this study, we introduce an experimental model of human skin grafted to NOD-SCID IL2R\u03b3null mice. In this model, we demonstrate that xenografting leads to the transient loss of LC from the human skin grafts. Despite the lack of a human hematopoietic system, human LC repopulated the xenografts 6 to 9 wk after transplantation. By staining of LC with the proliferation marker Ki67, we show that one third of the replenishing LC exhibit proliferative activity in vivo. We further used the skin xenograft as an in vivo model for human GVHD. HLA-disparate third-party T cells stimulated with skin donor-derived dendritic cells were injected intravenously into NOD-SCID IL2R\u03b3null mice that had been transplanted with human skin. The application of alloreactive T cells led to erythema and was associated with histological signs of GVHD limited to the transplanted human skin. The inflammation also led to the depletion of LC from the epidermis. In summary, we provide evidence that human LC are able to repopulate the skin independent of blood-derived precursor cells and that this at least partly relates to their proliferative capacity. Our data also propose xeno-transplantation of human skin as a model system for studying the role of skin dendritic cells in the efferent arm of GVHD.<\/jats:p>","DOI":"10.4049\/jimmunol.1001491","type":"journal-article","created":{"date-parts":[[2011,6,23]],"date-time":"2011-06-23T03:13:04Z","timestamp":1308798784000},"page":"1142-1149","source":"Crossref","is-referenced-by-count":19,"title":["Human Epidermal Langerhans Cells Replenish Skin Xenografts and Are Depleted by Alloreactive T Cells In Vivo"],"prefix":"10.1093","volume":"187","author":[{"given":"Julia","family":"Hemmerling","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Wegner-Kops","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"von Stebut","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo F","family":"Hartwig","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya C","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Children's Hospital T\u00fcbingen , 72076 T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Theobald","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf E","family":"Schopf","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Herr","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf G","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz , 55131 Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,1]]},"reference":[{"key":"2025032410261015700_r1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/jid.2008.225","article-title":"Resident and \u201cinflammatory\u201d dendritic cells in human skin","volume":"129","author":"Zaba","year":"2009","journal-title":"J. Invest. Dermatol."},{"key":"2025032410261015700_r2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nri2455","article-title":"Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells","volume":"8","author":"Merad","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025032410261015700_r3","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/282324a0","article-title":"Epidermal Langerhans cells are derived from cells originating in bone marrow","volume":"282","author":"Katz","year":"1979","journal-title":"Nature"},{"key":"2025032410261015700_r4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/282321a0","article-title":"Mouse epidermal Ia molecules have a bone marrow origin","volume":"282","author":"Frelinger","year":"1979","journal-title":"Nature"},{"key":"2025032410261015700_r5","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/ni852","article-title":"Langerhans cells renew in the skin throughout life under steady-state conditions","volume":"3","author":"Merad","year":"2002","journal-title":"Nat. Immunol."},{"key":"2025032410261015700_r6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1600-0609.2005.00595.x","article-title":"Complete donor chimaerism of Langerhans cells in lymph node early after allogeneic bone marrow transplantation","volume":"76","author":"Ikeda","year":"2006","journal-title":"Eur. J. Haematol."},{"key":"2025032410261015700_r7","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1126\/science.285.5426.412","article-title":"Prevention of graft versus host disease by inactivation of host antigen-presenting cells","volume":"285","author":"Shlomchik","year":"1999","journal-title":"Science"},{"key":"2025032410261015700_r8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/BF02473310","article-title":"Combined immunophenotyping and FISH with sex chromosome-specific DNA probes for the detection of chimerism in epidermal Langerhans cells after sex-mismatched bone marrow transplantation","volume":"106","author":"Hessel","year":"1996","journal-title":"Histochem. Cell Biol."},{"key":"2025032410261015700_r9","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.4049\/jimmunol.136.4.1210","article-title":"Effects of physicochemical agents on murine epidermal Langerhans cells and Thy-1-positive dendritic epidermal cells","volume":"136","author":"Aberer","year":"1986","journal-title":"J. Immunol."},{"key":"2025032410261015700_r10","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/nm1038","article-title":"Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease","volume":"10","author":"Merad","year":"2004","journal-title":"Nat. Med."},{"key":"2025032410261015700_r11","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1182\/blood.V99.4.1442","article-title":"Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients","volume":"99","author":"Auffermann-Gretzinger","year":"2002","journal-title":"Blood"},{"key":"2025032410261015700_r12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1084\/jem.20051787","article-title":"The fate of human Langerhans cells in hematopoietic stem cell transplantation","volume":"203","author":"Collin","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025032410261015700_r13","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1182\/blood-2006-03-005769","article-title":"Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation","volume":"109","author":"Meyer","year":"2007","journal-title":"Blood"},{"key":"2025032410261015700_r14","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nri2017","article-title":"Humanized mice in translational biomedical research","volume":"7","author":"Shultz","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"2025032410261015700_r15","doi-asserted-by":"crossref","first-page":"6477","DOI":"10.4049\/jimmunol.174.10.6477","article-title":"Human lymphoid and myeloid cell development in NOD\/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells","volume":"174","author":"Shultz","year":"2005","journal-title":"J. Immunol."},{"key":"2025032410261015700_r16","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/0888-7543(91)90139-6","article-title":"PCR amplification of chromosome-specific alpha satellite DNA: definition of centromeric STS markers and polymorphic analysis","volume":"11","author":"Warburton","year":"1991","journal-title":"Genomics"},{"key":"2025032410261015700_r17","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/bmt.2009.212","article-title":"Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation","volume":"45","author":"Meyer","year":"2010","journal-title":"Bone Marrow Transplant."},{"key":"2025032410261015700_r18","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.4049\/jimmunol.170.8.4069","article-title":"Mature dendritic cells derived from human monocytes within 48 hours: a novel strategy for dendritic cell differentiation from blood precursors","volume":"170","author":"Dauer","year":"2003","journal-title":"J. Immunol."},{"key":"2025032410261015700_r19","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.exphem.2007.12.011","article-title":"Acute myeloid leukemia (AML)-reactive cytotoxic T lymphocyte clones rapidly expanded from CD8(+) CD62L((high)+) T cells of healthy donors prevent AML engraftment in NOD\/SCID IL2Rgamma(null) mice","volume":"36","author":"Distler","year":"2008","journal-title":"Exp. Hematol."},{"key":"2025032410261015700_r20","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00262-004-0616-7","article-title":"A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia virus Ankara (MVA-hTyr)","volume":"54","author":"Meyer","year":"2005","journal-title":"Cancer Immunol. Immunother."},{"key":"2025032410261015700_r21","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1111\/j.1600-6143.2008.02401.x","article-title":"The programmed death (PD)-1\/PD-ligand 1 pathway regulates graft-versus-host-reactive CD8 T cells after liver transplantation","volume":"8","author":"Schuchmann","year":"2008","journal-title":"Am. J. Transplant."},{"key":"2025032410261015700_r22","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/sj.jid.5700807","article-title":"Mouse models of psoriasis","volume":"127","author":"Gudjonsson","year":"2007","journal-title":"J. Invest. Dermatol."},{"key":"2025032410261015700_r23","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1084\/jem.20031482","article-title":"Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha","volume":"199","author":"Boyman","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032410261015700_r24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cyto.2005.07.011","article-title":"Cytokines and Langerhans cell mobilisation in mouse and man","volume":"32","author":"Griffiths","year":"2005","journal-title":"Cytokine"},{"key":"2025032410261015700_r25","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1073\/pnas.80.6.1650","article-title":"Biology of Langerhans cells: selective migration of Langerhans cells into allogeneic and xenogeneic grafts on nude mice","volume":"80","author":"Krueger","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410261015700_r26","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/1523-1747.ep12261453","article-title":"Biology of Langerhans cells: analysis by experiments to deplete Langerhans cells from human skin","volume":"82","author":"Krueger","year":"1984","journal-title":"J. Invest. Dermatol."},{"key":"2025032410261015700_r27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/1523-1747.ep12464659","article-title":"Further evidence for the self-reproducing capacity of Langerhans cells in human skin","volume":"88","author":"Czernielewski","year":"1987","journal-title":"J. Invest. Dermatol."},{"key":"2025032410261015700_r28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/376037a0","article-title":"Identification and inhibition of the ICE\/CED-3 protease necessary for mammalian apoptosis","volume":"376","author":"Nicholson","year":"1995","journal-title":"Nature"},{"key":"2025032410261015700_r29","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1177\/002215540205000401","article-title":"Improved detection of apoptotic cells in archival paraffin sections: immunohistochemistry using antibodies to cleaved caspase 3","volume":"50","author":"Gown","year":"2002","journal-title":"J. Histochem. Cytochem."},{"key":"2025032410261015700_r30","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1046\/j.1523-1747.2002.01742.x","article-title":"Epidermal langerhans cell depletion after artificial ultraviolet B irradiation of human skin in vivo: apoptosis versus migration","volume":"118","author":"K\u00f6lgen","year":"2002","journal-title":"J. Invest. Dermatol."},{"key":"2025032410261015700_r31","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1751-1097.2007.00284.x","article-title":"DNA damage, apoptosis and langerhans cells\u2014activators of UV-induced immune tolerance","volume":"84","author":"Timares","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"2025032410261015700_r32","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/ni1307","article-title":"Langerhans cells arise from monocytes in vivo","volume":"7","author":"Ginhoux","year":"2006","journal-title":"Nat. Immunol."},{"key":"2025032410261015700_r33","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1046\/j.1523-1747.1998.00162.x","article-title":"The human hair follicle: a reservoir of CD40+ B7-deficient Langerhans cells that repopulate epidermis after UVB exposure","volume":"110","author":"Gilliam","year":"1998","journal-title":"J. Invest. Dermatol."},{"key":"2025032410261015700_r34","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1084\/jem.20091586","article-title":"Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network","volume":"206","author":"Chorro","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032410261015700_r35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1084\/jem.20081747","article-title":"HLA-DR+ leukocytes acquire CD1 antigens in embryonic and fetal human skin and contain functional antigen-presenting cells","volume":"206","author":"Schuster","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032410261015700_r36","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.4049\/jimmunol.177.7.4414","article-title":"Host-derived Langerhans cells persist after MHC-matched allografting independent of donor T cells and critically influence the alloresponses mediated by donor lymphocyte infusions","volume":"177","author":"Durakovic","year":"2006","journal-title":"J. Immunol."},{"key":"2025032410261015700_r37","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1097\/01.tp.0000203318.16224.57","article-title":"Fast appearance of donor dendritic cells in human skin: dynamics of skin and blood dendritic cells after allogeneic hematopoietic cell transplantation","volume":"81","author":"Auffermann-Gretzinger","year":"2006","journal-title":"Transplantation"},{"key":"2025032410261015700_r38","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1084\/jem.20081633","article-title":"Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation","volume":"206","author":"Haniffa","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032410261015700_r39","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1182\/blood-2002-10-3241","article-title":"A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-\/- gammac-\/- double-mutant mice","volume":"102","author":"van Rijn","year":"2003","journal-title":"Blood"},{"key":"2025032410261015700_r40","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/S0301-472X(99)00111-3","article-title":"An in vivo model of human skin acute graft-versus-host disease: transplantation of cultured human epidermal cells and dermal fibroblasts with human lymphocytes into SCID mice","volume":"27","author":"Takakura","year":"1999","journal-title":"Exp. Hematol."},{"key":"2025032410261015700_r41","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/S0301-472X(01)00639-7","article-title":"Injection of CD4(+) and CD8(+) cells with donor or host accessory cells induces acute graft-vs-host disease in human skin in immunodeficient mice","volume":"29","author":"Matsumoto","year":"2001","journal-title":"Exp. Hematol."},{"key":"2025032410261015700_r42","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1182\/blood-2007-09-112789","article-title":"Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs","volume":"111","author":"Beilhack","year":"2008","journal-title":"Blood"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/3\/1142\/62476328\/1001491.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/3\/1142\/62476328\/1001491.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T02:53:55Z","timestamp":1743130435000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/187\/3\/1142\/8087904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,1]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1001491","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,8]]},"published":{"date-parts":[[2011,8,1]]}}}