title: Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease.
abstract: The presentation pathways by which allogeneic peptides induce graft-versus-host disease (GVHD) are unclear. We developed a bone marrow transplant (BMT) system in mice whereby presentation of a processed recipient peptide within major histocompatibility complex (MHC) class II molecules could be spatially and temporally quantified. Whereas donor antigen presenting cells (APCs) could induce lethal acute GVHD via MHC class II, recipient APCs were 100-1,000 times more potent in this regard. After myeloablative irradiation, T cell activation and memory differentiation occurred in lymphoid organs independently of alloantigen. Unexpectedly, professional hematopoietic-derived recipient APCs within lymphoid organs had only a limited capacity to induce GVHD, and dendritic cells were not required. In contrast, nonhematopoietic recipient APCs within target organs induced universal GVHD mortality and promoted marked alloreactive donor T cell expansion within the gastrointestinal tract and inflammatory cytokine generation. These data challenge current paradigms, suggesting that experimental lethal acute GVHD can be induced by nonhematopoietic recipient APCs.
authors: The Queensland Institute of Medical Research, Brisbane, Australia.
authors: Motoko
authors: M
authors: Koyama
authors: Rachel D
authors: RD
authors: Kuns
authors: Stuart D
authors: SD
authors: Olver
authors: Neil C
authors: NC
authors: Raffelt
authors: Yana A
authors: YA
authors: Wilson
authors: Alistair L J
authors: AL
authors: Don
authors: Katie E
authors: KE
authors: Lineburg
authors: Melody
authors: M
authors: Cheong
authors: Renee J
authors: RJ
authors: Robb
authors: Kate A
authors: KA
authors: Markey
authors: Antiopi
authors: A
authors: Varelias
authors: Bernard
authors: B
authors: Malissen
authors: Günter J
authors: GJ
authors: Hämmerling
authors: Andrew D
authors: AD
authors: Clouston
authors: Christian R
authors: CR
authors: Engwerda
authors: Purnima
authors: P
authors: Bhat
authors: Kelli P A
authors: KP
authors: MacDonald
authors: Geoffrey R
authors: GR
authors: Hill
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D006413:Hematopoietic System / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D060053:Transplant Donor Site; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II