|
|
Blood, 1 December 2004, Vol. 104, No. 12, pp. 3829-3835.
Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-01-0393.
Previous Article | Next Article 
Submitted February 2, 2004
Accepted July 13, 2004
Absence of Clinical GVHD and the In Vivo Induction of Regulatory T cells following Facilitating Cell Transplantation
Yolonda L Colson*, Kenneth Christopher, Jonathan Glickman, Kendra N Taylor, Renee Wright, and David L Perkins
Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA
Laboratory of Molecular Immunology, Renal Division, Brigham and Women's Hospital, Boston, MA, USA
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
* Corresponding author; email: ycolson{at}partners.org.
Abstract
Graft-versus-host disease (GVHD) and failure of engraftment limit clinical bone marrow transplantation (BMT) to patients with a closely matched donor. Engraftment failure of purified allogeneic hematopoietic stem cells (HSC) has been decreased in various BMT models by including donor BM-derived CD8+/   TCR- facilitating cells (FC) or CD8+/ TCR+ T cells in the BM inoculum. To aggressively investigate GVHD potential of these donor CD8+ populations, a purified cell model of lethal GVHD was established in a murine semiallogeneic parent F1 combination. Lethally irradiated recipients were reconstituted with purified donor HSC alone, or in combination with splenic T cells (TSP), BM-derived T cells (TBM), or the FC population. In marked contrast to the lethal GVHD present in recipients of HSC plus TSP or CD8+ TBM, recipients of donor HSC+FC inocula did not exhibit significant clinical or histologic evidence of GVHD. Instead, HSC+FC recipients were characterized by increased splenocyte expression of TGF and the induction of the regulatory T cell genes, CTLA4, GITR and FoxP3. These findings suggest that the FC, which express a unique FCp33-TCR heterodimer in place of  TCR, permits HSC alloengraftment and prevents GVHD through the novel approach of regulatory T cell induction in vivo.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
T. Fehr, S. Wang, F. Haspot, J. Kurtz, P. Blaha, T. Hogan, M. Chittenden, T. Wekerle, and M. Sykes
Rapid Deletional Peripheral CD8 T Cell Tolerance Induced by Allogeneic Bone Marrow: Role of Donor Class II MHC and B Cells
J. Immunol.,
September 15, 2008;
181(6):
4371 - 4380.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Huang, I. J. Fugier-Vivier, T. Miller, M. J. Elliott, H. Xu, L. D. Bozulic, P. M. Chilton, and S. T. Ildstad
Plasmacytoid Precursor Dendritic Cells From NOD Mice Exhibit Impaired Function: Are They a Component of Diabetes Pathogenesis?
Diabetes,
September 1, 2008;
57(9):
2360 - 2370.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. N. Taylor, V. R. Shinde-Patil, E. Cohick, and Y. L. Colson
Induction of FoxP3+CD4+25+ Regulatory T Cells Following Hemopoietic Stem Cell Transplantation: Role of Bone Marrow-Derived Facilitating Cells
J. Immunol.,
August 15, 2007;
179(4):
2153 - 2162.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. N. Taylor, V. R. Shinde Patil, and Y. L. Colson
Reconstitution of Allogeneic Hemopoietic Stem Cells: The Essential Role of FcR{gamma} and the TCR beta-Chain-FCp33 Complex
J. Immunol.,
August 1, 2006;
177(3):
1444 - 1450.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D.-P. Lu, L. Dong, T. Wu, X.-J. Huang, M.-J. Zhang, W. Han, H. Chen, D.-H. Liu, Z.-Y. Gao, Y.-H. Chen, et al.
Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation
Blood,
April 15, 2006;
107(8):
3065 - 3073.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Rieger, C. Loddenkemper, J. Maul, T. Fietz, D. Wolff, H. Terpe, B. Steiner, E. Berg, S. Miehlke, M. Bornhauser, et al.
Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD
Blood,
February 15, 2006;
107(4):
1717 - 1723.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. J. Fugier-Vivier, F. Rezzoug, Y. Huang, A. J. Graul-Layman, C. L. Schanie, H. Xu, P. M. Chilton, and S. T. Ildstad
Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment
J. Exp. Med.,
February 7, 2005;
201(3):
373 - 383.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|