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Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.
- Source :
-
Blood [Blood] 2016 Aug 11; Vol. 128 (6), pp. 794-804. Date of Electronic Publication: 2016 Jun 23. - Publication Year :
- 2016
-
Abstract
- Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD.<br /> (© 2016 by The American Society of Hematology.)
- Subjects :
- Acute Disease
Adoptive Transfer
Animals
Chronic Disease
Dendritic Cells immunology
Graft vs Host Disease etiology
Graft vs Host Disease immunology
Graft vs Host Disease therapy
Histocompatibility Antigens Class II immunology
Lymphocyte Count
Mice
Mice, Inbred BALB C
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory transplantation
Antigen Presentation
Bone Marrow Transplantation adverse effects
Dendritic Cells pathology
Graft vs Host Disease pathology
T-Lymphocytes, Regulatory pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 128
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 27338097
- Full Text :
- https://doi.org/10.1182/blood-2015-11-680876