|
|
Blood, 1 February 2005, Vol. 105, No. 3, pp. 1355-1361.
Prepublished online as a Blood First Edition Paper on September 30, 2004; DOI 10.1182/blood-2004-08-3305.
 Previous Article | Next Article 
Submitted August 25, 2004
Accepted September 25, 2004
Prevention of lethal acute GVHD with an agonistic CD28 antibody and rapamycin
Michael H Albert, Xue-Zhong Yu, Paul J Martin, and Claudio Anasetti*
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Dr. von Haunersches Children's Hospital, Ludwig-Maximilians-University, Munich, Germany
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA
* Corresponding author; email: anasetc{at}moffitt.usf.edu.
Successful hematopoietic cell transplantation (HCT) from an allogeneic donor should ideally produce tolerance to recipient alloantigens while preserving anti-infectious and anti-tumor immunity. Rapamycin together with costimulation blockade can induce tolerance in organ allograft models by inhibiting G1  S phase progression and promoting T cell apoptosis. In contrast to blocking costimulation through CD28, administration of agonistic CD28-specific antibody 37.51 partially prevents lethal graft-versus-host disease (GVHD) by selective depletion of alloreactive T cells in mice.1 We hypothesized that combining rapamycin with agonistic CD28 treatment would improve GVHD control by tolerizing a small subset of alloreactive T cells that might escape effects of the CD28-specific antibody. A short course of rapamycin plus agonistic CD28 treatment showed synergism at suboptimal doses, was highly effective in preventing lethal GVHD, and was superior to rapamycin plus CD28 blockade in an MHC class I and II-mismatched HCT model. The combination treatment reduced the number of proliferating, alloreactive cells in the recipient, promoted donor B and T cell reconstitution and reduced inflammatory cytokine levels. Administration of rapamycin plus agonistic CD28 antibodies offers a promising new therapeutic approach to facilitate tolerance after HCT.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Mariotti, J. Foley, U. Jung, T. Borenstein, N. Kantardzic, S. Han, J. T. Hanson, E. Wong, N. Buxhoeveden, J. B. Trepel, et al.
Ex Vivo Rapamycin Generates Apoptosis-Resistant Donor Th2 Cells That Persist In Vivo and Prevent Hemopoietic Stem Cell Graft Rejection
J. Immunol.,
January 1, 2008;
180(1):
89 - 105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Zeiser, D. B. Leveson-Gower, E. A. Zambricki, N. Kambham, A. Beilhack, J. Loh, J.-Z. Hou, and R. S. Negrin
Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells
Blood,
January 1, 2008;
111(1):
453 - 462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Z. Yu, Y. Liang, R. I. Nurieva, F. Guo, C. Anasetti, and C. Dong
Opposing Effects of ICOS on Graft-versus-Host Disease Mediated by CD4 and CD8 T Cells.
J. Immunol.,
June 15, 2006;
176(12):
7394 - 7401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. R Blazar and W. J Murphy
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD)
Phil Trans R Soc B,
September 29, 2005;
360(1461):
1747 - 1767.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
