|
|
Blood, 15 October 2008, Vol. 112, No. 8, pp. 3508-3516.
Prepublished online as a Blood First Edition Paper on July 9, 2008; DOI 10.1182/blood-2007-09-113670.
 Previous Article | Next Article 
Submitted September 19, 2007
Accepted June 27, 2008
TLR agonists regulate alloresponses and uncover a critical role for donor APCs in allogeneic bone marrow rejection
Patricia A Taylor, Michael J Ehrhardt, Christopher J Lees, Angela Panoskaltsis-Mortari, Arthur M Krieg, Arlene H Sharpe, William J Murphy, Jonathan S Serody, Hiroaki Hemmi, Shizuo Akira, Robert B Levy, and Bruce R Blazar*
Cancer Center and the Department of Pediatrics, Divn of BMT, University of Minnesota, Minneapolis, MN, United States
Pfizer, Cambridge, MA, United States
Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States
Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV, United States
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States
Dept of Host Defense, Research Inst. for Microbial Disease, Osaka University, Osaka, Japan
Department of Microbiology and Immunology, University of Miami, Miami, FL, United States
* Corresponding author; email: blaza001{at}umn.edu.
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 GVHD lethality by TLR9 ligation of host APCs, dependent upon host IFN but independent of host IL-12, IL-6 or NK cells. Imaging studies showed significantly more GFP+ effector T cells in lymphoid and non-lymphoid organs. In engraftment studies, CpG ODNs promoted allogeneic donor BM rejection independent of host IFN, 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 anti-donor 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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Donor dendritic cells dance the do-si-do in allogeneic transplantation
- Edmund K. Waller and Jian-Ming Li
Blood 2008 112: 3007-3008.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
L. Chen, E. Ahmed, T. Wang, Y. Wang, J. Ochando, A. S. Chong, and M.-L. Alegre
TLR Signals Promote IL-6/IL-17-Dependent Transplant Rejection
J. Immunol.,
May 15, 2009;
182(10):
6217 - 6225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wilson, H. Cullup, R. Lourie, Y. Sheng, A. Palkova, K. J. Radford, A. M. Dickinson, A. M. Rice, D. N.J. Hart, and D. J. Munster
Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease
J. Exp. Med.,
February 16, 2009;
206(2):
387 - 398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
