|
|
Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-06-1649.
Submitted June 5, 2002
Accepted January 16, 2003
NON-MYELOABLATIVE CONDITIONING IS SUFFICIENT TO ALLOW ENGRAFTMENT OF EGFP-EXPRESSING BONE MARROW AND SUBSEQUENT ACCEPTANCE OF EGFP-TRANSGENIC SKIN GRAFTS IN MICE
Goran Andersson, Ben M W Illigens, Kevin W Johnson, David Calderhead, Christian LeGuern, Gilles Benichou, Mary E White-Scharf, and Julian D Down*
Department of Hematology, BioTransplant Incorporated, Boston, MA, USA
Cellular and Molecular Immunology Laboratory, Schepens Eye Research Institute, Boston, MA, USA
Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA, USA
* Corresponding author; email: jddown{at}earthlink.net.
Immunological reactions against gene therapy products may prove to be a frequent problem in clinical gene therapy protocols. Enhanced green fluorescent protein (EGFP) is commonly used as a marker in gene transfer protocols and immune responses against EGFP-expressing cells have been documented. The present study was designed to investigate the effect of a pharmacological, non-myeloablative, conditioning regimen on the development of EGFP+ donor/recipient mixed bone marrow chimerism and ensuing tolerance to EGFP expressing transplants. To this end, C57BL/6J (B6) mice were treated with soluble formulations of either busulfan (Busulfex®) or the closely related compound treosulfan, followed by transplantation of bone marrow cells from EGFP-transgenic (B6-EGFP.Tg) donor mice. Such conditioning regimens resulted in long-term persistence of donor EGFP+ cells among various hematopoietic lineages from blood, bone marrow and thymus. Stable hematopoietic chimeras transplanted at 10-17 weeks after bone marrow transplantation (BMT) with B6-EGFP.Tg skin grafts all accepted their transplants while non-EGFP chimeric B6 control animals were able to mount rejection of the EGFP+ B6 skin grafts. Control third party grafts from MHC-mismatched mice were rejected within 20 days indicating that acceptance of EGFP-expressing skin grafts was the result of specific immune tolerance induction by the transplant of EGFP-transgenic bone marrow. Long-term tolerance to EGFP in chimeric recipients was confirmed by the absence of anti-EGFP reactive T cells and antibodies. These results and broaden the therapeutic potential for using hematopoietic molecular chimerism in non-myeloablated recipients as a means of preventing rejection of genetically modified cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. M. Ide, B. Gangadharan, K.-Y. Chiang, C. B. Doering, and H. T. Spencer
Hematopoietic stem-cell gene therapy of hemophilia A incorporating a porcine factor VIII transgene and nonmyeloablative conditioning regimens
Blood,
October 15, 2007;
110(8):
2855 - 2863.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Weng, J. Dyson, and F. Dazzi
Low-intensity transplant regimens facilitate recruitment of donor-specific regulatory T cells that promote hematopoietic engraftment
PNAS,
May 15, 2007;
104(20):
8415 - 8420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mostoslavsky, A. J. Fabian, S. Rooney, F. W. Alt, and R. C. Mulligan
Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer
PNAS,
October 31, 2006;
103(44):
16406 - 16411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.-A. Gross, P. Chappert, M. Leboeuf, V. Monteilhet, L. Van Wittenberghe, O. Danos, and J. Davoust
Simple conditioning with monospecific CD4+CD25+ regulatory T cells for bone marrow engraftment and tolerance to multiple gene products
Blood,
September 15, 2006;
108(6):
1841 - 1848.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V Tepavcevic and W.F Blakemore
Glial grafting for demyelinating disease
Phil Trans R Soc B,
September 29, 2005;
360(1461):
1775 - 1795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
