Promoting regulation via the inhibition of DNAM-1 after transplantation

Koyama, Motoko, Kuns, Rachel D., Olver, Stuart D., Lineburg, Katie E., Lor, Mary, Teal, Bianca E., Raffelt, Neil C., Leveque, Lucie, Chan, Christopher J., Robb, Renee J., Markey, Kate A., Alexander, Kylie A., Varelias, Antiopi, Clouston, Andrew D., Smyth, Mark J., MacDonald, Kelli P.A. and Hill, Geoffrey R. (2013) Promoting regulation via the inhibition of DNAM-1 after transplantation. Blood, 121 17: 3511-3520. doi:10.1182/blood-2012-07-444026

Author Koyama, Motoko
Kuns, Rachel D.
Olver, Stuart D.
Lineburg, Katie E.
Lor, Mary
Teal, Bianca E.
Raffelt, Neil C.
Leveque, Lucie
Chan, Christopher J.
Robb, Renee J.
Markey, Kate A.
Alexander, Kylie A.
Varelias, Antiopi
Clouston, Andrew D.
Smyth, Mark J.
MacDonald, Kelli P.A.
Hill, Geoffrey R.
Title Promoting regulation via the inhibition of DNAM-1 after transplantation
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
Publication date 2013-04-25
Sub-type Article (original research)
DOI 10.1182/blood-2012-07-444026
Volume 121
Issue 17
Start page 3511
End page 3520
Total pages 10
Place of publication Washington DC United States
Publisher American Society of Hematology
Collection year 2014
Language eng
Formatted abstract
Donor T cells play pivotal roles in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects following bone marrow transplantation (BMT). DNAX accessory molecule 1 (DNAM-1) is a costimulatory and adhesion molecule, expressed mainly by natural killer cells and CD8+ T cells at steady state to promote adhesion to ligand-expressing targets and enhance cytolysis. We have analyzed the role of this pathway in GVHD and GVL. The absence of DNAM-1 on the donor graft attenuated GVHD in major histocompatibility complex (MHC)-mismatched and MHC-matched BMT following conditioning with lethal and sublethal irradiation. In contrast, DNAM-1 was not critical for GVL effects against ligand (CD155) expressing and nonexpressing leukemia. The effects on GVHD following myeloablative conditioning were independent of CD8+ T cells and dependent on CD4+ T cells, and specifically donor FoxP3+ regulatory T cells (Treg). The absence of DNAM-1 promoted the expansion and suppressive function of Treg after BMT. These findings provide support for therapeutic DNAM-1 inhibition to promote tolerance in relevant inflammatory-based diseases characterized by T-cell activation.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 30 Jan 2014, 21:11:02 EST by Matthew Lamb on behalf of School of Medicine