Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease

Koyama, Motoko, Kuns, Rachel D., Olver, Stuart D., Raffelt, Neil C., Wilson, Yana A., Don, Alistair L. J., Lineburg, Katie E., Cheong, Melody, Robb, Renee J., Markey, Kate A., Varelias, Antiopi, Malissen, Bernard, Hammerling, Gunter J., Clouston, Andrew D., Engwerda, Christian R., Bhat, Purnima, MacDonald, Kelli P. A. and Hill, Geoffrey R. (2012) Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease. Nature Medicine, 18 1: 135-142. doi:10.1038/nm.2597


Author Koyama, Motoko
Kuns, Rachel D.
Olver, Stuart D.
Raffelt, Neil C.
Wilson, Yana A.
Don, Alistair L. J.
Lineburg, Katie E.
Cheong, Melody
Robb, Renee J.
Markey, Kate A.
Varelias, Antiopi
Malissen, Bernard
Hammerling, Gunter J.
Clouston, Andrew D.
Engwerda, Christian R.
Bhat, Purnima
MacDonald, Kelli P. A.
Hill, Geoffrey R.
Title Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease
Journal name Nature Medicine   Check publisher's open access policy
ISSN 1078-8956
1546-170X
Publication date 2012-01
Year available 2011
Sub-type Article (original research)
DOI 10.1038/nm.2597
Volume 18
Issue 1
Start page 135
End page 142
Total pages 8
Place of publication New York, United States
Publisher Nature Publishing Group
Collection year 2012
Language eng
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 hematopoieticderived 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 29 November 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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