PMID- 14742992 OWN - NLM STAT- MEDLINE DCOM- 20040227 LR - 20181130 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 77 IP - 2 DP - 2004 Jan 27 TI - Allogeneic reaction induces dendritic cell maturation through proinflammatory cytokine secretion. PG - 267-75 AB - BACKGROUND: A bone marrow transplantation conditioning regimen is known to activate host dendritic cells (DC), which then become able to initiate graft-versus-host disease (GVHD) by presenting alloantigens. In this article, the authors addressed whether the alloreaction could reciprocally maintain DC in an activation state through secretion of proinflammatory cytokines. METHODS: Skin biopsy specimens from GVHD patients were analyzed for the presence of DC. Supernatants collected from primary major histocompatibility antigen (allogeneic mixed leukocyte reaction [MLR] supernatant [SN]) or secondary minor histocompatibility antigen-mismatched mixed lymphocyte reactions were used to culture cytokine-promoted immature (im) DC. DC phenotype, function, and migration were analyzed. RESULTS: Immunostaining from GVHD skin biopsy specimens showed a deficit of Langerhans cells (LC) in the epidermis but the presence of mature DC in the dermis. Because LC should have recovered in the epidermis by this time, the authors then addressed whether the allogeneic reaction could maintain DC in an activation and migratory state, through secretion of inflammatory cytokines. With this aim, cytokine-mediated imDC were exposed to alloMLR-SN for 2 days. The authors observed that DC increased their expression of CD80, CD86, CD40, and human leukocyte antigen (HLA)-DR and neoexpressed CD83, DC-LAMP/CD208, and CCR7. At the functional level, alloMLR-SN-treated DC lost their ability to capture dextran, improved their allostimulatory capacity, and migrated in response to macrophage inflammatory protein 3beta. Interestingly, SN collected from secondary HLA-identical but minor histocompatibility antigen-mismatched MLR induced almost equivalent DC phenotypic maturation. CONCLUSIONS: The authors' results show that the allogeneic reaction leads to maturation and migration of DC through proinflammatory cytokine secretion. This might contribute to the impairment of LC reconstitution in the skin of patients with GVHD. FAU - Laurin, David AU - Laurin D AD - Cell Therapy and Immunology Department, Etablissement Francais du Sang Rhone-Alpes, Lyon, France. FAU - Kanitakis, Jean AU - Kanitakis J FAU - Bienvenu, Jacques AU - Bienvenu J FAU - Bardin, Christine AU - Bardin C FAU - Bernaud, Jeanine AU - Bernaud J FAU - Lebecque, Serge AU - Lebecque S FAU - Gebuhrer, Lucette AU - Gebuhrer L FAU - Rigal, Dominique AU - Rigal D FAU - Eljaafari, Assia AU - Eljaafari A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Antigens, CD) RN - 0 (Antigens, Surface) RN - 0 (CD207 protein, human) RN - 0 (Cytokines) RN - 0 (HLA-DR Antigens) RN - 0 (Interleukins) RN - 0 (Lectins, C-Type) RN - 0 (Mannose-Binding Lectins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antigens, CD MH - Antigens, Surface/analysis MH - Biopsy MH - Blood Donors MH - Cell Differentiation/drug effects/immunology MH - Cytokines/*metabolism/*pharmacology MH - Dendritic Cells/drug effects/*physiology MH - Graft vs Host Disease/*immunology/pathology MH - HLA-DR Antigens/analysis MH - Humans MH - Inflammation/physiopathology MH - Interferon-gamma/metabolism MH - Interleukins/metabolism MH - Lectins, C-Type/analysis MH - Lymphocyte Culture Test, Mixed MH - Mannose-Binding Lectins/analysis MH - Monocytes/cytology/drug effects/*immunology MH - Reference Values MH - Skin/immunology/pathology MH - Transplantation, Homologous/*immunology MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2004/01/27 05:00 MHDA- 2004/02/28 05:00 CRDT- 2004/01/27 05:00 PHST- 2004/01/27 05:00 [pubmed] PHST- 2004/02/28 05:00 [medline] PHST- 2004/01/27 05:00 [entrez] AID - 10.1097/01.TP.0000101006.39475.41 [doi] PST - ppublish SO - Transplantation. 2004 Jan 27;77(2):267-75. doi: 10.1097/01.TP.0000101006.39475.41.