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Science 16 July 1999:
Vol. 285. no. 5426, pp. 412 - 415
DOI: 10.1126/science.285.5426.412
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Reports

Prevention of Graft Versus Host Disease by Inactivation of Host Antigen-Presenting Cells

Warren D. Shlomchik, 1 Matthew S. Couzens, 1 Cheng Bi Tang, 1 Jennifer McNiff, 3 Marie E. Robert, 4 Jinli Liu, 56 Mark J. Shlomchik, 56* Stephen G. Emerson 12*dagger

Graft versus host disease, an alloimmune attack on host tissues mounted by donor T cells, is the most important toxicity of allogeneic bone marrow transplantation. The mechanism by which allogeneic T cells are initially stimulated is unknown. In a murine allogeneic bone marrow transplantation model it was found that, despite the presence of numerous donor antigen-presenting cells, only host-derived antigen-presenting cells initiated graft versus host disease. Thus, strategies for preventing graft versus host disease could be developed that are based on inactivating host antigen-presenting cells. Such strategies could expand the safety and application of allogeneic bone marrow transplantation in treatment of common genetic and neoplastic diseases.

1 Department of Medicine, Hematology and Oncology Division,
2 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
3 Department of Dermatology,
4 Department of Pathology,
5 Department of Laboratory Medicine,
6 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: emersons{at}mail.med.upenn.edu

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Identification of the Immunodominant HY H2-Dk Epitope and Evaluation of the Role of Direct and Indirect Antigen Presentation in HY Responses.
M. Millrain, D. Scott, C. Addey, H. Dewchand, P. Ellis, I. Ehrmann, M. Mitchell, P. Burgoyne, E. Simpson, and J. Dyson (2005)
J. Immunol. 175, 7209-7217
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Up-regulated expression in nonhematopoietic tissues of the BCL2A1-derived minor histocompatibility antigens in response to inflammatory cytokines: relevance for allogeneic immunotherapy of leukemia.
F. M. Kloosterboer, S. A. P. van Luxemburg-Heijs, R. A. van Soest, H. M. E. van Egmond, R. Willemze, and J. H. F. Falkenburg (2005)
Blood 106, 3955-3957
   Abstract »    Full Text »    PDF »
CD11chigh Dendritic Cell Ablation Impairs Lymphopenia-Driven Proliferation of Naive and Memory CD8+ T Cells.
T. Zaft, A. Sapoznikov, R. Krauthgamer, D. R. Littman, and S. Jung (2005)
J. Immunol. 175, 6428-6435
   Abstract »    Full Text »    PDF »
Ex Vivo Expanded Dendritic Cells Home to T-Cell Zones of Lymphoid Organs and Survive in Vivo after Allogeneic Bone Marrow Transplantation.
C. H. Schimmelpfennig, S. Schulz, C. Arber, J. Baker, I. Tarner, J. McBride, C. H. Contag, and R. S. Negrin (2005)
Am. J. Pathol. 167, 1321-1331
   Abstract »    Full Text »    PDF »
Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease.
C. A. Wysocki, Q. Jiang, A. Panoskaltsis-Mortari, P. A. Taylor, K. P. McKinnon, L. Su, B. R. Blazar, and J. S. Serody (2005)
Blood 106, 3300-3307
   Abstract »    Full Text »    PDF »
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
B. R Blazar and W. J Murphy (2005)
Phil Trans R Soc B 360, 1747-1767
   Abstract »    Full Text »    PDF »
Inhibition of Natural Type I IFN-Producing and Dendritic Cell Development by a Small Molecule Receptor Tyrosine Kinase Inhibitor with Flt3 Affinity.
R. Tussiwand, N. Onai, L. Mazzucchelli, and M. G. Manz (2005)
J. Immunol. 175, 3674-3680
   Abstract »    Full Text »    PDF »
HANGING IN THE BALANCE: KIR and Their Role in Disease.
A. P. Williams, A. R. Bateman, and S. I. Khakoo (2005)
Mol. Interv. 5, 226-240
   Abstract »    Full Text »    PDF »
In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets.
A. Beilhack, S. Schulz, J. Baker, G. F. Beilhack, C. B. Wieland, E. I. Herman, E. M. Baker, Y.-A. Cao, C. H. Contag, and R. S. Negrin (2005)
Blood 106, 1113-1122
   Abstract »    Full Text »    PDF »
Host {gamma}{delta} T cells: an innate bridge to the epithelial targets of GVHD?.
G. R. Hill (2005)
Blood 106, 393-394
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Critical role of host {gamma}{delta} T cells in experimental acute graft-versus-host disease.
Y. Maeda, P. Reddy, K. P. Lowler, C. Liu, D. K. Bishop, and J. L. M. Ferrara (2005)
Blood 106, 749-755
   Abstract »    Full Text »    PDF »
CCR6 regulates CD4+ T-cell-mediated acute graft-versus-host disease responses.
R. Varona, V. Cadenas, L. Gomez, C. Martinez-A, and G. Marquez (2005)
Blood 106, 18-26
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Cytotoxic minor histocompatibility antigen HA-1-specific CD8+ effector memory T cells: artificial APCs pave the way for clinical application by potent primary in vitro induction.
K. Schilbach, G. Kerst, S. Walter, M. Eyrich, D. Wernet, R. Handgretinger, W. Xie, H.-G. Rammensee, I. Muller, H.-J. Buhring, et al. (2005)
Blood 106, 144-149
   Abstract »    Full Text »    PDF »
Curcumin Inhibits Immunostimulatory Function of Dendritic Cells: MAPKs and Translocation of NF-{kappa}B as Potential Targets.
G.-Y. Kim, K.-H. Kim, S.-H. Lee, M.-S. Yoon, H.-J. Lee, D.-O. Moon, C.-M. Lee, S.-C. Ahn, Y. C. Park, and Y.-M. Park (2005)
J. Immunol. 174, 8116-8124
   Abstract »    Full Text »    PDF »
Emergent autoimmunity in graft-versus-host disease.
E. Tivol, R. Komorowski, and W. R. Drobyski (2005)
Blood 105, 4885-4891
   Abstract »    Full Text »    PDF »
New approaches for preventing and treating chronic graft-versus-host disease.
S. J. Lee (2005)
Blood 105, 4200-4206
   Abstract »    Full Text »    PDF »
TGF-{beta}-dependent CD103 expression by CD8+ T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease.
R. El-Asady, R. Yuan, K. Liu, D. Wang, R. E. Gress, P. J. Lucas, C. B. Drachenberg, and G. A. Hadley (2005)
J. Exp. Med. 201, 1647-1657
   Abstract »    Full Text »    PDF »


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