| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;
Transplantation Research Center, Brigham and Women’s Hospital and Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115;
Department of Molecular Immunology, Tokyo Medical and Dental University, Tokyo, Japan; and
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
Programmed death-1 (PD-1) is a negative costimulatory molecule, and blocking the interaction of PD-1 with its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), enhances autoimmune disease in several animal models. We have studied the role of PD-1 ligands in disease susceptibility and chronic progression in experimental autoimmune encephalomyelitis (EAE). In BALB/c mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35–55, PD-L1 but not PD-L2 blockade significantly increased EAE incidence. In B10.S mice immunized with myelin proteolipid protein (PLP) peptide 139–151, both PD-L1 and PD-L2 blockade markedly enhanced EAE severity. In prediabetic NOD mice immunized with PLP48-70, PD-L2 blockade worsened EAE but did not induce diabetes, whereas PD-L1 blockade precipitated diabetes but did not worsen EAE, suggesting different regulatory roles of these two ligands in EAE and diabetes. B6 mice immunized with MOG35-55 developed chronic persistent EAE, and PD-L2 blockade in the chronic phase exacerbated EAE, whereas PD-L1 blockade did not. In contrast, SJL/J mice immunized with PLP139-151 developed chronic relapsing-remitting EAE, and only PD-L1 blockade during remission precipitated EAE relapse. The strain-specific effects of PD-1 ligand blockade did not correlate with the expression of PD-L1 and PD-L2 on dendritic cells and macrophages in lymphoid tissue, or on inflammatory cells in the CNS. However, EAE enhancement is correlated with less prominent Th2 cytokine induction after specific PD-1 ligand blockade. In conclusion, PD-L1 and PD-L2 differentially regulate the susceptibility and chronic progression of EAE in a strain-specific manner.
This article has been cited by other articles:
|
|
 |
|
  N. Mozaffarian, A. E. Wiedeman, and A. M. Stevens Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1 Rheumatology, July 23, 2008; (2008) ken256v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lafon, F. Megret, S. G. Meuth, O. Simon, M. L. Velandia Romero, M. Lafage, L. Chen, L. Alexopoulou, R. A. Flavell, C. Prehaud, et al. Detrimental Contribution of the Immuno-Inhibitor B7-H1 to Rabies Virus Encephalitis J. Immunol., June 1, 2008; 180(11): 7506 - 7515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yang, J. Popoola, S. Khandwala, N. Vadivel, V. Vanguri, X. Yuan, S. Dada, I. Guleria, C. Tian, M. J. Ansari, et al. Critical Role of Donor Tissue Expression of Programmed Death Ligand-1 in Regulating Cardiac Allograft Rejection and Vasculopathy Circulation, February 5, 2008; 117(5): 660 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Menke, J. A. Lucas, G. C. Zeller, M. E. Keir, X. R. Huang, N. Tsuboi, T. N. Mayadas, H. Y. Lan, A. H. Sharpe, and V. R. Kelley Programmed Death 1 Ligand (PD-L) 1 and PD-L2 Limit Autoimmune Kidney Disease: Distinct Roles J. Immunol., December 1, 2007; 179(11): 7466 - 7477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zhu, Y. Bando, S. Xiao, K. Yang, A. C. Anderson, V. K. Kuchroo, and S. J. Khoury CD11b+Ly-6Chi Suppressive Monocytes in Experimental Autoimmune Encephalomyelitis J. Immunol., October 15, 2007; 179(8): 5228 - 5237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Goldberg, C. H. Maris, E. L. Hipkiss, A. S. Flies, L. Zhen, R. M. Tuder, J. F. Grosso, T. J. Harris, D. Getnet, K. A. Whartenby, et al. Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells Blood, July 1, 2007; 110(1): 186 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kaneko, J. Wang, M. Kaneko, G. Yiu, J. M. Hurrell, T. Chitnis, S. J. Khoury, and Z. He Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J. Neurosci., September 20, 2006; 26(38): 9794 - 9804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, Y. Chung, C. Bishop, B. Daugherty, H. Chute, P. Holst, C. Kurahara, F. Lott, N. Sun, A. A. Welcher, et al. Regulation of T cell activation and tolerance by PDL2 PNAS, August 1, 2006; 103(31): 11695 - 11700. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
