| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Immunology, National Children’s Medical Research Center, Tokyo;
Department of Internal Medicine, Division of Rheumatology, and
Department of Immunology, Juntendo University School of Medicine, Tokyo; and
§
Department of Immunobiology, Research Institute for Biological Science, Science University of Tokyo, Chiba, Japan
The blockade of B7, using B7 antagonists such as anti-CD80 and/or -CD86 mAbs or CTLA4Ig in vivo, has been shown to induce an efficient suppression of T cell-mediated immune responses in allograft, allergy, and autoimmune models. However, this treatment does not result in complete tolerance. In this study, we examined CD28-B7-independent activation pathways in the pathogenesis of graft-vs-host disease (GVHD) using allogeneic T cells from CD28-deficient mice. Acute GVHD was induced in the absence of CD28 on donor T cells and its manifestations were obvious in the lymphoid tissues. The CD28-independent GVHD was significantly improved by treatment with anti-CD40 ligand (CD40L) mAb. In contrast, treatment with anti-CD80 plus anti-CD86 mAbs exacerbated the clinical manifestations of GVHD and increased the T cell response against host alloantigen, resulting in the expression of CTLA4, CD40L, and CD25 on splenic T cells. These data suggested that the CD40L-CD40 pathway significantly contributed to the CD28-independent pathogenesis of acute GVHD, whereas the CTLA4-B7 pathway acted protectively in the development of GVHD. These results imply that selectively blockading CD28, instead of disrupting both CD28 and CTLA4, would be a better therapeutic strategy for GVHD. Additionally, the simultaneous use of CD40 antagonists may be advantageous.
This article has been cited by other articles:
|
|
 |
|
  B. Verbinnen, A. D. Billiau, J. Vermeiren, G. Galicia, D. M. A. Bullens, L. Boon, P. Cadot, G. Hens, C. Dewolf-Peeters, S. W. Van Gool, et al. Contribution of Regulatory T Cells and Effector T Cell Deletion in Tolerance Induction by Costimulation Blockadel J. Immunol., July 15, 2008; 181(2): 1034 - 1042. [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]
|
|
|
|
 |
|
 J. Tsukada, A. Ozaki, T. Hanada, T. Chinen, R. Abe, A. Yoshimura, and M. Kubo The role of suppressor of cytokine signaling 1 as a negative regulator for aberrant expansion of CD8{alpha}+ dendritic cell subset Int. Immunol., September 1, 2005; 17(9): 1167 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Blazar, A. H. Sharpe, A. I. Chen, A. Panoskaltsis-Mortari, C. Lees, H. Akiba, H. Yagita, N. Killeen, and P. A. Taylor Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogeneic bone marrow transplant recipients Blood, May 1, 2003; 101(9): 3741 - 3748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Taylor, C. J. Lees, H. Waldmann, R. J. Noelle, and B. R. Blazar Requirements for the promotion of allogeneic engraftment by anti-CD154 (anti-CD40L) monoclonal antibody under nonmyeloablative conditions Blood, July 15, 2001; 98(2): 467 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Blazar, B. S. Kwon, A. Panoskaltsis-Mortari, K. B. Kwak, J. J. Peschon, and P. A. Taylor Ligation of 4-1BB (CDw137) Regulates Graft-Versus-Host Disease, Graft-Versus-Leukemia, and Graft Rejection in Allogeneic Bone Marrow Transplant Recipients J. Immunol., March 1, 2001; 166(5): 3174 - 3183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Lu, S. Sakamaki, H. Kuroda, T. Kusakabe, Y. Konuma, T. Akiyama, A. Fujimi, N. Takemoto, K. Nishiie, T. Matsunaga, et al. Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603 Blood, February 15, 2001; 97(4): 1123 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhan, A. J. Corbett, J. L. Brady, R. M. Sutherland, and A. M. Lew CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation J. Immunol., October 1, 2000; 165(7): 3612 - 3619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Masteller, E. Chuang, A. C. Mullen, S. L. Reiner, and C. B. Thompson Structural Analysis of CTLA-4 Function In Vivo J. Immunol., May 15, 2000; 164(10): 5319 - 5327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. Villegas, U. Wille, L. Craig, P. S. Linsley, D. M. Rennick, R. Peach, and C. A. Hunter Blockade of Costimulation Prevents Infection-Induced Immunopathology in Interleukin-10-Deficient Mice Infect. Immun., May 1, 2000; 68(5): 2837 - 2844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Z. Yu, S. J. Bidwell, P. J. Martin, and C. Anasetti CD28-Specific Antibody Prevents Graft-Versus-Host Disease in Mice J. Immunol., May 1, 2000; 164(9): 4564 - 4568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tsukada, H. Akiba, T. Kobata, Y. Aizawa, H. Yagita, and K. Okumura Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation Blood, April 1, 2000; 95(7): 2434 - 2439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Reichmann, W. Walker, E. N. Villegas, L. Craig, G. Cai, J. Alexander, and C. A. Hunter The CD40/CD40 Ligand Interaction Is Required for Resistance to Toxoplasmic Encephalitis Infect. Immun., March 1, 2000; 68(3): 1312 - 1318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Blair, J. L. Riley, D. M. Harlan, R. Abe, D. K. Tadaki, S. C. Hoffmann, L. White, T. Francomano, S. J. Perfetto, A. D. Kirk, et al. Cd40 Ligand (Cd154) Triggers a Short-Term Cd4+ T Cell Activation Response That Results in Secretion of Immunomodulatory Cytokines and Apoptosis J. Exp. Med., February 21, 2000; 191(4): 651 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sakurai, J. Ohata, K. Saito, H. Miyajima, T. Hirano, T. Kohsaka, S. Enomoto, K. Okumura, and M. Azuma Blockade of CTLA-4 Signals Inhibits Th2-Mediated Murine Chronic Graft-Versus-Host Disease by an Enhanced Expansion of Regulatory CD8+ T Cells J. Immunol., January 15, 2000; 164(2): 664 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yin, L. Zhang, R. Wang, L. Radvanyi, C. Haudenschild, Q. Fang, M. R. Kehry, and Y. Shi Ligation of CD28 In Vivo Induces CD40 Ligand Expression and Promotes B Cell Survival J. Immunol., October 15, 1999; 163(8): 4328 - 4334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Chambers, M. S. Kuhns, and J. P. Allison Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4+ T cell responses PNAS, July 20, 1999; 96(15): 8603 - 8608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Kenyon, M. Chatzipetrou, M. Masetti, A. Ranuncoli, M. Oliveira, J. L. Wagner, A. D. Kirk, D. M. Harlan, L. C. Burkly, and C. Ricordi Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154 PNAS, July 6, 1999; 96(14): 8132 - 8137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Blazar, P. A. Taylor, A. Panoskaltsis-Mortari, A. H. Sharpe, and D. A. Vallera Opposing Roles of CD28:B7 and CTLA-4:B7 Pathways in Regulating In Vivo Alloresponses in Murine Recipients of MHC Disparate T Cells J. Immunol., June 1, 1999; 162(11): 6368 - 6377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Brunner, C. A. Chambers, F. K.-M. Chan, J. Hanke, A. Winoto, and J. P. Allison CTLA-4-Mediated Inhibition of Early Events of T Cell Proliferation J. Immunol., May 15, 1999; 162(10): 5813 - 5820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.A. CHAMBERS and J.P. ALLISON CTLA-4 -- The Costimulatory Molecule That Doesn't: Regulation of T-cell Responses by Inhibition Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 303 - 312. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
