Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease
- 29 November 2011
- journal article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 18 (1), 135-142
- https://doi.org/10.1038/nm.2597
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.This publication has 43 references indexed in Scilit:
- A repertoire-independent and cell-intrinsic defect in murine GVHD induction by effector memory T cellsBlood, 2011
- Langerhans cells are not required for graft-versus-host diseaseBlood, 2011
- An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammationBlood, 2010
- Recipient B Cells Are Not Required for Graft-Versus-Host Disease InductionTransplantation and Cellular Therapy, 2010
- CD47 Is Required for Suppression of Allograft Rejection by Donor-Specific TransfusionThe Journal of Immunology, 2010
- PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activityGastroenterology, 2008
- Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cellsBlood, 2008
- Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organsBlood, 2008
- Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponseBlood, 2006
- Preterminal host dendritic cells in irradiated mice prime CD8+ T cell–mediated acute graft-versus-host diseaseJCI Insight, 2002