Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 12 January 2001:
Vol. 291. no. 5502, pp. 319 - 322
DOI: 10.1126/science.291.5502.319
Prev | Table of Contents

Reports

Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice

Hiroyuki Nishimura,1 Taku Okazaki,1 Yoshimasa Tanaka,2 Kazuki Nakatani,6 Masatake Hara,3 Akira Matsumori,3 Shigetake Sasayama,3 Akira Mizoguchi,4 Hiroshi Hiai,5 Nagahiro Minato,2 Tasuku Honjo1*

Dilated cardiomyopathy is a severe pathology of the heart with poorly understood etiology. Disruption of the gene encoding the negative immunoregulatory receptor PD-1 in BALB/c mice, but not in BALB/c RAG-2-/- mice, caused dilated cardiomyopathy with severely impaired contraction and sudden death by congestive heart failure. Affected hearts showed diffuse deposition of immunoglobulin G (IgG) on the surface of cardiomyocytes. All of the affected PD-1-/- mice exhibited high-titer circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes. These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases.

1 Department of Medical Chemistry,
2 Department of Immunology and Cell Biology,
3 Department of Cardiovascular Medicine,
4 Department of Anatomy and Neurobiology,
5 Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo, Kyoto, 606-8501, Japan.
6 Second Department of Anatomy, Osaka City University Medical School, 1-4-3 Asahi-Machi, Abeno-Ku, Osaka, 545-8585, Japan.
*   To whom correspondence should be addressed. E-mail: honjo{at}mfour.med.kyoto-u.ac.jp

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Human decidual stromal cells suppress cytokine secretion by allogenic CD4+ T cells via PD-1 ligand interactions.
T. Nagamatsu, D. J. Schust, J. Sugimoto, and B. F. Barrier (2009)
Hum. Reprod. 24, 3160-3171
   Abstract »    Full Text »    PDF »
Recruitment of Sprouty1 to Immune Synapse Regulates T Cell Receptor Signaling.
J. S. Lee, J. E. Lee, Y. M. Oh, J. B. Park, H. Choi, C. Y. Choi, I.-H. Kim, S. H. Lee, and K. Choi (2009)
J. Immunol. 183, 7178-7186
   Abstract »    Full Text »    PDF »
Reviving Function in CD4+ T Cells Adapted to Persistent Systemic Antigen.
M. N. Rivas, K. Weatherly, M. Hazzan, B. Vokaer, S. Dremier, F. Gaudray, M. Goldman, I. Salmon, and M. Y. Braun (2009)
J. Immunol. 183, 4284-4291
   Abstract »    Full Text »    PDF »
PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model.
L. Zhang, T. F. Gajewski, and J. Kline (2009)
Blood 114, 1545-1552
   Abstract »    Full Text »    PDF »
Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression.
S. Mumprecht, C. Schurch, J. Schwaller, M. Solenthaler, and A. F. Ochsenbein (2009)
Blood 114, 1528-1536
   Abstract »    Full Text »    PDF »
Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired.
M. Ahmadzadeh, L. A. Johnson, B. Heemskerk, J. R. Wunderlich, M. E. Dudley, D. E. White, and S. A. Rosenberg (2009)
Blood 114, 1537-1544
   Abstract »    Full Text »    PDF »
PD-1 on dendritic cells impedes innate immunity against bacterial infection.
S. Yao, S. Wang, Y. Zhu, L. Luo, G. Zhu, S. Flies, H. Xu, W. Ruff, M. Broadwater, I.-H. Choi, et al. (2009)
Blood 113, 5811-5818
   Abstract »    Full Text »    PDF »
T-Cell Suppression by Programmed Cell Death 1 Ligand 1 on Retinal Pigment Epithelium during Inflammatory Conditions.
S. Sugita, Y. Usui, S. Horie, Y. Futagami, H. Aburatani, T. Okazaki, T. Honjo, M. Takeuchi, and M. Mochizuki (2009)
Invest. Ophthalmol. Vis. Sci. 50, 2862-2870
   Abstract »    Full Text »    PDF »
PD-1-Mediated Suppression of IL-2 Production Induces CD8+ T Cell Anergy In Vivo.
S. Chikuma, S. Terawaki, T. Hayashi, R. Nabeshima, T. Yoshida, S. Shibayama, T. Okazaki, and T. Honjo (2009)
J. Immunol. 182, 6682-6689
   Abstract »    Full Text »    PDF »
Accelerated Course of Experimental Autoimmune Encephalomyelitis in PD-1-Deficient Central Nervous System Myelin Mutants.
A. Kroner, N. Schwab, C. W. Ip, S. Ortler, K. Gobel, K.-A. Nave, M. Maurer, R. Martini, and H. Wiendl (2009)
Am. J. Pathol. 174, 2290-2299
   Abstract »    Full Text »    PDF »
PD-1/PD-L Blockade Prevents Anergy Induction and Enhances the Anti-Tumor Activities of Glycolipid-Activated Invariant NKT Cells.
V. V. Parekh, S. Lalani, S. Kim, R. Halder, M. Azuma, H. Yagita, V. Kumar, L. Wu, and L. Van Kaer (2009)
J. Immunol. 182, 2816-2826
   Abstract »    Full Text »    PDF »
Human Corneal Endothelial Cells Expressing Programmed Death-Ligand 1 (PD-L1) Suppress PD-1+ T Helper 1 Cells by a Contact-Dependent Mechanism.
S. Sugita, Y. Usui, S. Horie, Y. Futagami, Y. Yamada, J. Ma, T. Kezuka, H. Hamada, T. Usui, M. Mochizuki, et al. (2009)
Invest. Ophthalmol. Vis. Sci. 50, 263-272
   Abstract »    Full Text »    PDF »
IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection.
D. G. Brooks, S.-J. Ha, H. Elsaesser, A. H. Sharpe, G. J. Freeman, and M. B. A. Oldstone (2008)
PNAS 105, 20428-20433
   Abstract »    Full Text »    PDF »
Cutting Edge: Programmed Death-1/Programmed Death Ligand 1 Interaction Regulates the Induction and Maintenance of Invariant NKT Cell Anergy.
W.-S. Chang, J.-Y. Kim, Y.-J. Kim, Y.-S. Kim, J.-M. Lee, M. Azuma, H. Yagita, and C.-Y. Kang (2008)
J. Immunol. 181, 6707-6710
   Abstract »    Full Text »    PDF »
Identification of Cardiac Troponin I Sequence Motifs Leading to Heart Failure by Induction of Myocardial Inflammation and Fibrosis.
Z. Kaya, S. Goser, S. J. Buss, F. Leuschner, R. Ottl, J. Li, M. Volkers, S. Zittrich, G. Pfitzer, N. R. Rose, et al. (2008)
Circulation 118, 2063-2072
   Abstract »    Full Text »    PDF »
NFATc1 Regulates PD-1 Expression upon T Cell Activation.
K. J. Oestreich, H. Yoon, R. Ahmed, and J. M. Boss (2008)
J. Immunol. 181, 4832-4839
   Abstract »    Full Text »    PDF »
Expression and Function of PDCD1 at the Human Maternal-Fetal Interface.
E. S. Taglauer, A. S. Trikhacheva, J. G. Slusser, and M. G. Petroff (2008)
Biol Reprod 79, 562-569
   Abstract »    Full Text »    PDF »
Programmed Death Ligand 1 Regulates a Critical Checkpoint for Autoimmune Myocarditis and Pneumonitis in MRL Mice.
J. A. Lucas, J. Menke, W. A. Rabacal, F. J. Schoen, A. H. Sharpe, and V. R. Kelley (2008)
J. Immunol. 181, 2513-2521
   Abstract »    Full Text »    PDF »
From the Cover: Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2.
E. Lazar-Molnar, Q. Yan, E. Cao, U. Ramagopal, S. G. Nathenson, and S. C. Almo (2008)
PNAS 105, 10483-10488
   Abstract »    Full Text »    PDF »
Functional Tolerance of CD8+ T Cells Induced by Muscle-Specific Antigen Expression.
S. Calbo, H. Delagreverie, C. Arnoult, F.-J. Authier, F. Tron, and O. Boyer (2008)
J. Immunol. 181, 408-417
   Abstract »    Full Text »    PDF »
Protective Role of Programmed Death 1 Ligand 1 (PD-L1)in Nonobese Diabetic Mice: The Paradox in Transgenic Models.
C.-J. Wang, F.-C. Chou, C.-H. Chu, J.-C. Wu, S.-H. Lin, D.-M. Chang, and H.-K. Sytwu (2008)
Diabetes 57, 1861-1869
   Abstract »    Full Text »    PDF »
A Lupus-Suppressor BALB/c Locus Restricts IgG2 Autoantibodies without Altering Intrinsic B Cell-Tolerance Mechanisms.
T. Tarasenko, H. K. Kole, and S. Bolland (2008)
J. Immunol. 180, 3807-3814
   Abstract »    Full Text »    PDF »
PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice.
T. Yoshida, F. Jiang, T. Honjo, and T. Okazaki (2008)
PNAS 105, 3533-3538
   Abstract »    Full Text »    PDF »
The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors.
D. Y.-w. Lin, Y. Tanaka, M. Iwasaki, A. G. Gittis, H.-P. Su, B. Mikami, T. Okazaki, T. Honjo, N. Minato, and D. N. Garboczi (2008)
PNAS 105, 3011-3016
   Abstract »    Full Text »    PDF »
Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability.
T. Pentcheva-Hoang, L. Chen, D. M. Pardoll, and J. P. Allison (2007)
PNAS 104, 17765-17770
   Abstract »    Full Text »    PDF »
Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8+ T-Cell-Mediated Injury in the Heart.
N. Grabie, I. Gotsman, R. DaCosta, H. Pang, G. Stavrakis, M. J. Butte, M. E. Keir, G. J. Freeman, A. H. Sharpe, and A. H. Lichtman (2007)
Circulation 116, 2062-2071
   Abstract »    Full Text »    PDF »
Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation.
S.-J. Lin, C. D. Peacock, K. Bahl, and R. M. Welsh (2007)
J. Exp. Med. 204, 2321-2333
   Abstract »    Full Text »    PDF »
The B7 Family and Cancer Therapy: Costimulation and Coinhibition.
X. Zang and J. P. Allison (2007)
Clin. Cancer Res. 13, 5271-5279
   Abstract »    Full Text »    PDF »
PD-1 and PD-1 ligands: from discovery to clinical application.
T. Okazaki and T. Honjo (2007)
Int. Immunol.
   Abstract »    Full Text »    PDF »
Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function.
S. Terawaki, Y. Tanaka, T. Nagakura, T. Hayashi, S. Shibayama, K. Muroi, T. Okazaki, B. Mikami, D. N. Garboczi, T. Honjo, et al. (2007)
Int. Immunol.
   Abstract »    Full Text »    PDF »
Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy.
F. Tsushima, S. Yao, T. Shin, A. Flies, S. Flies, H. Xu, K. Tamada, D. M. Pardoll, and L. Chen (2007)
Blood 110, 180-185
   Abstract »    Full Text »    PDF »
Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells.
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. (2007)
Blood 110, 186-192
   Abstract »    Full Text »    PDF »
Roles of programmed death-1 (PD-1)/PD-1 ligands pathway in the development of murine acute myocarditis caused by coxsackievirus B3.
Y. Seko, H. Yagita, K. Okumura, M. Azuma, and R. Nagai (2007)
Cardiovasc Res 75, 158-167
   Abstract »    Full Text »    PDF »
T-cell co-stimulatory molecules: their role in allergic immune reactions.
T. Kallinich, K. C. Beier, U. Wahn, P. Stock, and E. Hamelmann (2007)
Eur. Respir. J. 29, 1246-1255
   Abstract »    Full Text »    PDF »
Fc{gamma} Receptors IIa on Cardiomyocytes and Their Potential Functional Relevance in Dilated Cardiomyopathy.
A. Staudt, P. Eichler, C. Trimpert, S. B. Felix, and A. Greinacher (2007)
J. Am. Coll. Cardiol. 49, 1684-1692
   Abstract »    Full Text »    PDF »
Cutting Edge: Programed Death (PD) Ligand-1/PD-1 Interaction Is Required for CD8+ T Cell Tolerance to Tissue Antigens.
N. Martin-Orozco, Y.-H. Wang, H. Yagita, and C. Dong (2006)
J. Immunol. 177, 8291-8295
   Abstract »    Full Text »    PDF »
Aberrant Regulation of Synovial T Cell Activation by Soluble Costimulatory Molecules in Rheumatoid Arthritis.
B. Wan, H. Nie, A. Liu, G. Feng, D. He, R. Xu, Q. Zhang, C. Dong, and J. Z. Zhang (2006)
J. Immunol. 177, 8844-8850
   Abstract »    Full Text »    PDF »
A Regulatory CD4+ T Cell Subset in the BB Rat Model of Autoimmune Diabetes Expresses Neither CD25 Nor Foxp3.
J.-L. Hillebrands, B. Whalen, J. T. J. Visser, J. Koning, K. D. Bishop, J. Leif, J. Rozing, J. P. Mordes, D. L. Greiner, and A. A. Rossini (2006)
J. Immunol. 177, 7820-7832
   Abstract »    Full Text »    PDF »
Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway.
B. T. Fife, I. Guleria, M. Gubbels Bupp, T. N. Eagar, Q. Tang, H. Bour-Jordan, H. Yagita, M. Azuma, M. H. Sayegh, and J. A. Bluestone (2006)
J. Exp. Med. 203, 2737-2747
   Abstract »    Full Text »    PDF »
B7-H1-Induced Apoptosis as a Mechanism of Immune Privilege of Corneal Allografts.
J. Hori, M. Wang, M. Miyashita, K. Tanemoto, H. Takahashi, T. Takemori, K. Okumura, H. Yagita, and M. Azuma (2006)
J. Immunol. 177, 5928-5935
   Abstract »    Full Text »    PDF »
Cardiac Troponin I but Not Cardiac Troponin T Induces Severe Autoimmune Inflammation in the Myocardium.
S. Goser, M. Andrassy, S. J. Buss, F. Leuschner, C. H. Volz, R. Ottl;, S. Zittrich;, N. Blaudeck, S. E. Hardt, G. Pfitzer, et al. (2006)
Circulation 114, 1693-1702
   Abstract »    Full Text »    PDF »
CD4+PD-1+ T Cells Acting as Regulatory Cells during the Induction of Anterior Chamber-Associated Immune Deviation..
Q. Meng, P. Yang, B. Li, H. Zhou, X. Huang, L. Zhu, Y. Ren, and A. Kijlstra (2006)
Invest. Ophthalmol. Vis. Sci. 47, 4444-4452
   Abstract »    Full Text »    PDF »
Generation and Characterization of B7-H4/B7S1/B7x-Deficient Mice..
W.-K. Suh, S. Wang, G. S. Duncan, Y. Miyazaki, E. Cates, T. Walker, B. U. Gajewska, E. Deenick, W. Dawicki, H. Okada, et al. (2006)
Mol. Cell. Biol. 26, 6403-6411
   Abstract »    Full Text »    PDF »
Regulation of T cell activation and tolerance by PDL2.
Y. Zhang, Y. Chung, C. Bishop, B. Daugherty, H. Chute, P. Holst, C. Kurahara, F. Lott, N. Sun, A. A. Welcher, et al. (2006)
PNAS 103, 11695-11700
   Abstract »    Full Text »    PDF »
T Cell Costimulation in the Development of Cardiac Allograft Vasculopathy: Potential Targets for Therapeutic Interventions.
M. Isobe, H. Kosuge, and J.-i. Suzuki (2006)
Arterioscler Thromb Vasc Biol 26, 1447-1456
   Abstract »    Full Text »    PDF »
CD4 T Cells Play Major Effector Role and CD8 T Cells Initiating Role in Spontaneous Autoimmune Myocarditis of HLA-DQ8 Transgenic IAb Knockout Nonobese Diabetic Mice..
S. L. Hayward, N. Bautista-Lopez, K. Suzuki, A. Atrazhev, P. Dickie, and J. F. Elliott (2006)
J. Immunol. 176, 7715-7725
   Abstract »    Full Text »    PDF »
B and T Lymphocyte Attenuator-Mediated Signal Transduction Provides a Potent Inhibitory Signal to Primary Human CD4 T Cells That Can Be Initiated by Multiple Phosphotyrosine Motifs..
J. M. Chemnitz, A. R. Lanfranco, I. Braunstein, and J. L. Riley (2006)
J. Immunol. 176, 6603-6614
   Abstract »    Full Text »    PDF »
Tissue expression of PD-L1 mediates peripheral T cell tolerance.
M. E. Keir, S. C. Liang, I. Guleria, Y. E. Latchman, A. Qipo, L. A. Albacker, M. Koulmanda, G. J. Freeman, M. H. Sayegh, and A. H. Sharpe (2006)
J. Exp. Med. 203, 883-895
   Abstract »    Full Text »    PDF »
High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals.
H. K. Kim, H. Guan, G. Zu, H. Li, L. Wu, X. Feng, C. Elmets, Y. Fu, and H. Xu (2006)
J. Leukoc. Biol. 79, 686-695
   Abstract »    Full Text »    PDF »
Cutting Edge: B and T Lymphocyte Attenuator and Programmed Death Receptor-1 Inhibitory Receptors Are Required for Termination of Acute Allergic Airway Inflammation.
C. Deppong, T. I. Juehne, M. Hurchla, L. D. Friend, D. D. Shah, C. M. Rose, T. L. Bricker, L. P. Shornick, E. C. Crouch, T. L. Murphy, et al. (2006)
J. Immunol. 176, 3909-3913
   Abstract »    Full Text »    PDF »
Trophoblast CD274 (B7-H1) Is Differentially Expressed Across Gestation: Influence of Oxygen Concentration.
L. M. Holets, J. S. Hunt, and M. G. Petroff (2006)
Biol Reprod 74, 352-358
   Abstract »    Full Text »    PDF »
Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice.
T. Okazaki, Y. Otaka, J. Wang, H. Hiai, T. Takai, J. V. Ravetch, and T. Honjo (2005)
J. Exp. Med. 202, 1643-1648
   Abstract »    Full Text »    PDF »
Programmed Death-1 (PD-1):PD-Ligand 1 Interactions Inhibit TCR-Mediated Positive Selection of Thymocytes.
M. E. Keir, Y. E. Latchman, G. J. Freeman, and A. H. Sharpe (2005)
J. Immunol. 175, 7372-7379
   Abstract »    Full Text »    PDF »
Differential Effects of B and T Lymphocyte Attenuator and Programmed Death-1 on Acceptance of Partially versus Fully MHC-Mismatched Cardiac Allografts.
R. Tao, L. Wang, R. Han, T. Wang, Q. Ye, T. Honjo, T. L. Murphy, K. M. Murphy, and W. W. Hancock (2005)
J. Immunol. 175, 5774-5782
   Abstract »    Full Text »    PDF »
Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis.
T. Yoshida, H. Hanawa, K. Toba, H. Watanabe, R. Watanabe, K. Yoshida, S. Abe, K. Kato, M. Kodama, and Y. Aizawa (2005)
Cardiovasc Res 68, 278-288
   Abstract »    Full Text »    PDF »
Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.
J. Wang, T. Yoshida, F. Nakaki, H. Hiai, T. Okazaki, and T. Honjo (2005)
PNAS 102, 11823-11828
   Abstract »    Full Text »    PDF »
The Immunomodulatory Proteins B7-DC, B7-H2, and B7-H3 Are Differentially Expressed across Gestation in the Human Placenta.
M. G. Petroff, E. Kharatyan, D. S. Torry, and L. Holets (2005)
Am. J. Pathol. 167, 465-473
   Abstract »    Full Text »    PDF »
Blockade of B7-H1 on Macrophages Suppresses CD4+ T Cell Proliferation by Augmenting IFN-{gamma}-Induced Nitric Oxide Production.
T. Yamazaki, H. Akiba, A. Koyanagi, M. Azuma, H. Yagita, and K. Okumura (2005)
J. Immunol. 175, 1586-1592
   Abstract »    Full Text »    PDF »
Analysis of the Role of Negative T Cell Costimulatory Pathways in CD4 and CD8 T Cell-Mediated Alloimmune Responses In Vivo.
T. Ito, T. Ueno, M. R. Clarkson, X. Yuan, M. M. Jurewicz, H. Yagita, M. Azuma, A. H. Sharpe, H. Auchincloss Jr, M. H. Sayegh, et al. (2005)
J. Immunol. 174, 6648-6656
   Abstract »    Full Text »    PDF »
Lymphocytes Are Not Required for the Rapid Onset of Coronary Heart Disease in Scavenger Receptor Class B Type I/Apolipoprotein E Double Knockout Mice.
S. L. Karackattu, M. H. Picard, and M. Krieger (2005)
Arterioscler Thromb Vasc Biol 25, 803-808
   Abstract »    Full Text »    PDF »
Role of the Programmed Death-1 Pathway in Regulation of Alloimmune Responses In Vivo.
S. E. Sandner, M. R. Clarkson, A. D. Salama, A. Sanchez-Fueyo, C. Domenig, A. Habicht, N. Najafian, H. Yagita, M. Azuma, L. A. Turka, et al. (2005)
J. Immunol. 174, 3408-3415
   Abstract »    Full Text »    PDF »
Microglial Expression of the B7 Family Member B7 Homolog 1 Confers Strong Immune Inhibition: Implications for Immune Responses and Autoimmunity in the CNS.
T. Magnus, B. Schreiner, T. Korn, C. Jack, H. Guo, J. Antel, I. Ifergan, L. Chen, F. Bischof, A. Bar-Or, et al. (2005)
J. Neurosci. 25, 2537-2546
   Abstract »    Full Text »    PDF »
The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo.
J. Liu, T. Miwa, B. Hilliard, Y. Chen, J. D. Lambris, A. D. Wells, and W.-C. Song (2005)
J. Exp. Med. 201, 567-577
   Abstract »    Full Text »    PDF »
Prevention of Experimental Autoimmune Encephalomyelitis by Transfer of Embryonic Stem Cell-Derived Dendritic Cells Expressing Myelin Oligodendrocyte Glycoprotein Peptide along with TRAIL or Programmed Death-1 Ligand.
S. Hirata, S. Senju, H. Matsuyoshi, D. Fukuma, Y. Uemura, and Y. Nishimura (2005)
J. Immunol. 174, 1888-1897
   Abstract »    Full Text »    PDF »
Blockade of B7-H1 and PD-1 by Monoclonal Antibodies Potentiates Cancer Therapeutic Immunity.
F. Hirano, K. Kaneko, H. Tamura, H. Dong, S. Wang, M. Ichikawa, C. Rietz, D. B. Flies, J. S. Lau, G. Zhu, et al. (2005)
Cancer Res. 65, 1089-1096
   Abstract »    Full Text »    PDF »
PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells.
Y. Iwai, S. Terawaki, and T. Honjo (2005)
Int. Immunol. 17, 133-144
   Abstract »    Full Text »    PDF »
The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation.
J. L. Riley and C. H. June (2005)
Blood 105, 13-21
   Abstract »    Full Text »    PDF »
Transgenic Expression of CTLA-4 Controls Lymphoproliferation in IL-2-Deficient Mice.
K. W. Hwang, W. B. Sweatt, M. Mashayekhi, D. A. Palucki, H. Sattar, E. Chuang, and M.-L. Alegre (2004)
J. Immunol. 173, 5415-5424
   Abstract »    Full Text »    PDF »
Blockade of the Interaction Between PD-1 and PD-L1 Accelerates Graft Arterial Disease in Cardiac Allografts.
N. Koga, J.-i. Suzuki, H. Kosuge, G. Haraguchi, Y. Onai, H. Futamatsu, Y. Maejima, R. Gotoh, H. Saiki, F. Tsushima, et al. (2004)
Arterioscler Thromb Vasc Biol 24, 2057-2062
   Abstract »    Full Text »    PDF »
Blocking Programmed Death-1 Ligand-PD-1 Interactions by Local Gene Therapy Results in Enhancement of Antitumor Effect of Secondary Lymphoid Tissue Chemokine.
Y.-F. He, G.-M. Zhang, X.-H. Wang, H. Zhang, Y. Yuan, D. Li, and Z.-H. Feng (2004)
J. Immunol. 173, 4919-4928
   Abstract »    Full Text »    PDF »
Murine B7-H3 Is a Negative Regulator of T Cells.
D. V. R. Prasad, T. Nguyen, Z. Li, Y. Yang, J. Duong, Y. Wang, and C. Dong (2004)
J. Immunol. 173, 2500-2506
   Abstract »    Full Text »    PDF »
Gene-Targeted Mice Lacking the Trex1 (DNase III) 3'->5' DNA Exonuclease Develop Inflammatory Myocarditis.
M. Morita, G. Stamp, P. Robins, A. Dulic, I. Rosewell, G. Hrivnak, G. Daly, T. Lindahl, and D. E. Barnes (2004)
Mol. Cell. Biol. 24, 6719-6727
   Abstract »    Full Text »    PDF »
Suppression of expression and function of negative immune regulator PD-1 by certain pattern recognition and cytokine receptor signals associated with immune system danger.
X. Zhong, C. Bai, W. Gao, T. B. Strom, and T. L. Rothstein (2004)
Int. Immunol. 16, 1181-1188
   Abstract »    Full Text »    PDF »
Acquisition of anergic and suppressive activities in transforming growth factor-{beta}-costimulated CD4+CD25- T cells.
H.-B. Park, D.-J. Paik, E. Jang, S. Hong, and J. Youn (2004)
Int. Immunol. 16, 1203-1213
   Abstract »    Full Text »    PDF »
PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells.
Y. E. Latchman, S. C. Liang, Y. Wu, T. Chernova, R. A. Sobel, M. Klemm, V. K. Kuchroo, G. J. Freeman, and A. H. Sharpe (2004)
PNAS 101, 10691-10696
   Abstract »    Full Text »    PDF »
SHP-1 and SHP-2 Associate with Immunoreceptor Tyrosine-Based Switch Motif of Programmed Death 1 upon Primary Human T Cell Stimulation, but Only Receptor Ligation Prevents T Cell Activation.
J. M. Chemnitz, R. V. Parry, K. E. Nichols, C. H. June, and J. L. Riley (2004)
J. Immunol. 173, 945-954
   Abstract »    Full Text »    PDF »
A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients.
C Nielsen, H Laustrup, A Voss, P Junker, S Husby, and S T Lillevang (2004)
Lupus 13, 510-516
   Abstract »    PDF »
Regulation of Postsurgical Fibrosis by the Programmed Death-1 Inhibitory Pathway.
M. A. Holsti, T. Chitnis, R. J. Panzo, R. T. Bronson, H. Yagita, M. H. Sayegh, and A. O. Tzianabos (2004)
J. Immunol. 172, 5774-5781
   Abstract »    Full Text »    PDF »
Altering immune tolerance therapeutically: the power of negative thinking.
G. J. Prud'homme (2004)
J. Leukoc. Biol. 75, 586-599
   Abstract »    Full Text »    PDF »
The genetic basis of systemic lupus erythematosus--knowledge of today and thoughts for tomorrow.
L. Prokunina and M. Alarcon-Riquelme (2004)
Hum. Mol. Genet. 13, R143-148
   Abstract »    Full Text »    PDF »
B7-DC Regulates Asthmatic Response by an IFN-{gamma}-Dependent Mechanism.
K. Matsumoto, H. Inoue, T. Nakano, M. Tsuda, Y. Yoshiura, S. Fukuyama, F. Tsushima, T. Hoshino, H. Aizawa, H. Akiba, et al. (2004)
J. Immunol. 172, 2530-2541
   Abstract »    Full Text »    PDF »
A Spontaneous Model for Autoimmune Myocarditis Using the Human MHC Molecule HLA-DQ8.
J. A. Taylor, E. Havari, M. F. McInerney, R. Bronson, K. W. Wucherpfennig, and M. A. Lipes (2004)
J. Immunol. 172, 2651-2658
   Abstract »    Full Text »    PDF »
PD-L1/B7H-1 Inhibits the Effector Phase of Tumor Rejection by T Cell Receptor (TCR) Transgenic CD8+ T Cells.
C. Blank, I. Brown, A. C. Peterson, M. Spiotto, Y. Iwai, T. Honjo, and T. F. Gajewski (2004)
Cancer Res. 64, 1140-1145
   Abstract »    Full Text »    PDF »
Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy.
B. S. Prabhakar, R. S. Bahn, and T. J. Smith (2003)
Endocr. Rev. 24, 802-835
   Abstract »    Full Text »    PDF »
Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IA{beta} knockout NOD mice.
J. F. Elliott, J. Liu, Z.-N. Yuan, N. Bautista-Lopez, S. L. Wallbank, K. Suzuki, D. Rayner, P. Nation, M. A. Robertson, G. Liu, et al. (2003)
PNAS 100, 13447-13452
   Abstract »    Full Text »    PDF »
Absence of Programmed Death Receptor 1 Alters Thymic Development and Enhances Generation of CD4/CD8 Double-Negative TCR-Transgenic T Cells.
C. Blank, I. Brown, R. Marks, H. Nishimura, T. Honjo, and T. F. Gajewski (2003)
J. Immunol. 171, 4574-4581
   Abstract »    Full Text »    PDF »
Blockade of B7-H1 Suppresses the Development of Chronic Intestinal Inflammation.
T. Kanai, T. Totsuka, K. Uraushihara, S. Makita, T. Nakamura, K. Koganei, T. Fukushima, H. Akiba, H. Yagita, K. Okumura, et al. (2003)
J. Immunol. 171, 4156-4163
   Abstract »    Full Text »    PDF »
T Cell Rewiring in Differentiation and Disease.
S. Krishnan, D. L. Farber, and G. C. Tsokos (2003)
J. Immunol. 171, 3325-3331
   Full Text »    PDF »
Vav1 Dephosphorylation by the Tyrosine Phosphatase SHP-1 as a Mechanism for Inhibition of Cellular Cytotoxicity.
C. C. Stebbins, C. Watzl, D. D. Billadeau, P. J. Leibson, D. N. Burshtyn, and E. O. Long (2003)
Mol. Cell. Biol. 23, 6291-6299
   Abstract »    Full Text »    PDF »
Blockade of Programmed Death-1 Engagement Accelerates Graft-Versus-Host Disease Lethality by an IFN-{gamma}-Dependent Mechanism.
B. R. Blazar, B. M. Carreno, A. Panoskaltsis-Mortari, L. Carter, Y. Iwai, H. Yagita, H. Nishimura, and P. A. Taylor (2003)
J. Immunol. 171, 1272-1277
   Abstract »    Full Text »    PDF »
PD-1 Inhibits Antiviral Immunity at the Effector Phase in the Liver.
Y. Iwai, S. Terawaki, M. Ikegawa, T. Okazaki, and T. Honjo (2003)
J. Exp. Med. 198, 39-50
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)