title: Allogeneic reaction induces dendritic cell maturation through proinflammatory cytokine secretion.
abstract: 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.
authors.affiliation: Cell Therapy and Immunology Department, Etablissement Français du Sang Rhône-Alpes, Lyon, France.
authors.forename: David
authors.initials: D
authors.lastname: Laurin
authors.forename: Jean
authors.initials: J
authors.lastname: Kanitakis
authors.forename: Jacques
authors.initials: J
authors.lastname: Bienvenu
authors.forename: Christine
authors.initials: C
authors.lastname: Bardin
authors.forename: Jeanine
authors.initials: J
authors.lastname: Bernaud
authors.forename: Serge
authors.initials: S
authors.lastname: Lebecque
authors.forename: Lucette
authors.initials: L
authors.lastname: Gebuhrer
authors.forename: Dominique
authors.initials: D
authors.lastname: Rigal
authors.forename: Assia
authors.initials: A
authors.lastname: Eljaafari
mesh_terms: D015703:Antigens, CD; D000954:Antigens, Surface / Q000032:analysis; D001706:Biopsy; D001782:Blood Donors; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D037181:Lectins, C-Type / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D037241:Mannose-Binding Lectins / Q000032:analysis; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D012016:Reference Values; D012867:Skin / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C121916:CD207 protein, human; D016207:Cytokines; D006684:HLA-DR Antigens; D007378:Interleukins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma