Immune insufficiency during GVHD is due to defective antigen presentation within dendritic cell subsets

Markey, Kate A., Koyama, Motoko, Kuns, Rachel D., Lineburg, Katie E., Wilson, Yana A., Olver, Stuart D., Raffelt, Neil C., Don, Alistair L. J., Varelias, Antiopi, Robb, Renee J., Cheong, Melody, Engwerda, Christian R., Steptoe, Raymond J., Ramshaw, Hayley S., Lopez, Angel F., Vega-Ramos, Javier, Lew, Andrew M., Villadangos, Jose A., Hill, Geoffrey R. and MacDonald, Kelli P. A. (2012) Immune insufficiency during GVHD is due to defective antigen presentation within dendritic cell subsets. Blood, 119 24: 5918-5930. doi:10.1182/blood-2011-12-398164

Author Markey, Kate A.
Koyama, Motoko
Kuns, Rachel D.
Lineburg, Katie E.
Wilson, Yana A.
Olver, Stuart D.
Raffelt, Neil C.
Don, Alistair L. J.
Varelias, Antiopi
Robb, Renee J.
Cheong, Melody
Engwerda, Christian R.
Steptoe, Raymond J.
Ramshaw, Hayley S.
Lopez, Angel F.
Vega-Ramos, Javier
Lew, Andrew M.
Villadangos, Jose A.
Hill, Geoffrey R.
MacDonald, Kelli P. A.
Title Immune insufficiency during GVHD is due to defective antigen presentation within dendritic cell subsets
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2012-06-14
Sub-type Article (original research)
DOI 10.1182/blood-2011-12-398164
Volume 119
Issue 24
Start page 5918
End page 5930
Total pages 13
Place of publication Washington, United States
Publisher American Society of Hematology
Collection year 2013
Language eng
Formatted abstract
Alloreactivity after transplantation is associated with profound immune suppression, and consequent opportunistic infection results in high morbidity and mortality. This immune suppression is most profound during GVHD after bone marrow transplantation where an inflammatory cytokine storm dominates. Contrary to current dogma, which avers that this is a T-cell defect, we demonstrate that the impairment lies within conventional dendritic cells (cDCs). Significantly, exogenous antigens can only be presented by the CD8 cDC subset after bone marrow transplantation, and inflammation during GVHD specifically renders the MHC class II presentation pathway in this population incompetent. In contrast, both classic and cross-presentation within MHC class I remain largely intact. Importantly, this defect in antigen processing can be partially reversed by TNF inhibition or the adoptive transfer of donor cDCs generated in the absence of inflammation.
Keyword Versus host disease
Bone marrow transplantation
Function in-vitro
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
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