Abstract:
:Cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODNs) are synthetic ODNs with unmethylated DNA sequences that mimic viral and bacterial DNA and protect against infectious agents and tumor challenge. We show that CpG ODNs markedly accelerated graft-versus-host disease (GVHD) lethality by Toll-like receptor 9 (TLR9) ligation of host antigen-presenting cells (APCs), dependent upon host IFNgamma but independent of host IL-12, IL-6, or natural killer (NK) cells. Imaging studies showed significantly more green fluorescent protein-positive (GFP(+)) effector T cells in lymphoid and nonlymphoid organs. In engraftment studies, CpG ODNs promoted allogeneic donor bone marrow (BM) rejection independent of host IFNgamma, IL-12, or IL-6. During the course of these studies, we uncovered a previously unknown and critical role of donor BM APCs in modulating the rejection response. CpG ODNs promoted BM rejection by ligation of donor BM, but not host, TLR9. CpG ODNs did not impair engraftment of TLR9(-/-) BM unless wild-type myeloid (CD11b(+)) but not B-lineage (CD19(+)) BM cells were added to the donor inoculum. The importance of donor BM APCs in modulating the strength of the host antidonor rejection response was underscored by the finding that B7-1/B7-2(-/-) BM was less likely than wild-type BM to be rejected. Collectively, these data offer new insight into the mechanism of alloresponses regulating GVHD and BM rejection.
journal_name
Bloodjournal_title
Bloodauthors
Taylor PA,Ehrhardt MJ,Lees CJ,Panoskaltsis-Mortari A,Krieg AM,Sharpe AH,Murphy WJ,Serody JS,Hemmi H,Akira S,Levy RB,Blazar BRdoi
10.1182/blood-2007-09-113670subject
Has Abstractpub_date
2008-10-15 00:00:00pages
3508-16issue
8eissn
0006-4971issn
1528-0020pii
blood-2007-09-113670journal_volume
112pub_type
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