|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 June 2002, Vol. 99, No. 12, pp. 4601-4609
TRANSPLANTATION
Tolerance induction of alloreactive T cells via ex vivo blockade
of the CD40:CD40L costimulatory pathway results in the generation of
a potent immune regulatory cell
Patricia A. Taylor,
Thea M. Friedman,
Robert Korngold,
Randolph J. Noelle, and
Bruce R. Blazar
From the University of Minnesota Cancer Center and
Department of Pediatrics, Division of Bone Marrow Transplantation,
Minneapolis; Kimmel Cancer Institute, Thomas Jefferson Medical College,
Philadelphia, PA; Department of Microbiology, Dartmouth Medical
College, Hanover, NH.
We previously reported that ex vivo blockade of the CD40:CD40L
costimulatory pathway in primary mixed lymphocyte reaction cultures resulted in profound in vitro secondary hyporesponsiveness and
30-fold or greater protection from graft-versus-host-disease (GVHD)
lethality. Present studies demonstrate that tolerance induction via
costimulatory blockade also results in the generation of a potent
immunoregulatory cell that inhibits both naive and primed alloresponses. The immunoregulatory capacity was dependent upon cell-to-cell contact that prevented the full activation of the naive or
primed cells. The inhibitory effect of tolerized cells did not preclude
the response of naive T cells to nominal protein antigen if antigen was
present at high concentration. However, under suboptimal antigen
concentration, nonspecific inhibition of responses occurred. The
tolerized regulatory cell population maintained a polyclonal T-cell
receptor V repertoire that was broader than in control
primed cultures. These data, the first to demonstrate that tolerance
induction via CD40:CD40L costimulatory blockade results in potent
regulatory function, are relevant to bone-marrow and solid-organ
transplantation. The generation of potent immunoregulatory capacity
during tolerization via CD40:CD40L blockade provides a fail-safe
mechanism to control alloreactive T cells that may have escaped
tolerization. These potent regulatory cells may be clinically
exploitable for the treatment and prevention of GVHD or autoimmunity.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Suzuki, X. Zheng, X. Zhang, M. Li, C. Vladau, T. E. Ichim, H. Sun, L. R. Min, B. Garcia, and W.-P. Min
Novel Vaccination for Allergy through Gene Silencing of CD40 Using Small Interfering RNA
J. Immunol.,
June 15, 2008;
180(12):
8461 - 8469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al.
A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique
Blood,
April 15, 2008;
111(8):
4392 - 4402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Jenkins, G. Perona-Wright, A. G. F. Worsley, N. Ishii, and A. S. MacDonald
Dendritic Cell Expression of OX40 Ligand Acts as a Costimulatory, Not Polarizing, Signal for Optimal Th2 Priming and Memory Induction In Vivo
J. Immunol.,
September 15, 2007;
179(6):
3515 - 3523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al.
Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease
Blood,
September 1, 2007;
110(5):
1689 - 1697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Duchmann and M Zeitz
T regulatory cell suppression of colitis: the role of TGF-{beta}
Gut,
May 1, 2006;
55(5):
604 - 606.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Bagenstose, R. K. Agarwal, P. B. Silver, D. M. Harlan, S. C. Hoffmann, R. L. Kampen, C.-C. Chan, and R. R. Caspi
Disruption of CD40/CD40-Ligand Interactions in a Retinal Autoimmunity Model Results in Protection without Tolerance
J. Immunol.,
July 1, 2005;
175(1):
124 - 130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Valzasina, C. Guiducci, H. Dislich, N. Killeen, A. D. Weinberg, and M. P. Colombo
Triggering of OX40 (CD134) on CD4+CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR
Blood,
April 1, 2005;
105(7):
2845 - 2851.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P. A. MacDonald, V. Rowe, A. D. Clouston, J. K. Welply, R. D. Kuns, J. L. M. Ferrara, R. Thomas, and G. R. Hill
Cytokine Expanded Myeloid Precursors Function as Regulatory Antigen-Presenting Cells and Promote Tolerance through IL-10-Producing Regulatory T Cells
J. Immunol.,
February 15, 2005;
174(4):
1841 - 1850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Weiss, V. Donkova-Petrini, L. Caccavelli, M. Balbo, C. Carbonneil, and Y. Levy
Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients
Blood,
November 15, 2004;
104(10):
3249 - 3256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Nagelkerken, I. Haspels, W. van Rijs, B. Blauw, J. L. Ferrant, D. M. Hess, E. A. Garber, F. R. Taylor, and L. C. Burkly
FcR Interactions Do Not Play a Major Role in Inhibition of Experimental Autoimmune Encephalomyelitis by Anti-CD154 Monoclonal Antibodies
J. Immunol.,
July 15, 2004;
173(2):
993 - 999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Vigouroux, E. Yvon, E. Biagi, and M. K. Brenner
Antigen-induced regulatory T cells
Blood,
July 1, 2004;
104(1):
26 - 33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Vermeiren, J. L. Ceuppens, M. Van Ghelue, P. Witters, D. Bullens, H. W. Mages, R. A. Kroczek, and S. W. Van Gool
Human T Cell Activation by Costimulatory Signal-Deficient Allogeneic Cells Induces Inducible Costimulator-Expressing Anergic T Cells with Regulatory Cell Activity
J. Immunol.,
May 1, 2004;
172(9):
5371 - 5378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-m. Chen, M. J. O'Shaughnessy, I. Gramaglia, A. Panoskaltsis-Mortari, W. J. Murphy, S. Narula, M. G. Roncarolo, and B. R. Blazar
IL-10 and TGF-{beta} induce alloreactive CD4+CD25- T cells to acquire regulatory cell function
Blood,
June 15, 2003;
101(12):
5076 - 5083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Sharp, C. Thompson, E. T. Samy, R. Noelle, and K. S. K. Tung
CD40 Ligand in Pathogenesis of Autoimmune Ovarian Disease of Day 3-Thymectomized Mice: Implication for CD40 Ligand Antibody Therapy
J. Immunol.,
February 15, 2003;
170(4):
1667 - 1674.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
