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Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease.
- Source :
-
Nature medicine [Nat Med] 2011 Nov 29; Vol. 18 (1), pp. 135-42. Date of Electronic Publication: 2011 Nov 29. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
Antigen Presentation immunology
Antigen-Presenting Cells cytology
Cytokines immunology
Dendritic Cells immunology
Hematopoietic System immunology
Humans
Lymphocyte Activation immunology
Mice
Mice, Inbred BALB C
Transplant Donor Site
Transplantation, Homologous
Antigen-Presenting Cells immunology
Bone Marrow Transplantation immunology
CD4-Positive T-Lymphocytes immunology
Graft vs Host Disease immunology
Histocompatibility Antigens Class II immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1546-170X
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 22127134
- Full Text :
- https://doi.org/10.1038/nm.2597