Genomes and Genes
Gene Symbol: Cd274
Description: CD274 antigen
Alias: A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1, programmed cell death 1 ligand 1, B7 homolog 1, PDCD1 ligand 1
- Parekh V, Lalani S, Kim S, Halder R, Azuma M, Yagita H, et al. PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J Immunol. 2009;182:2816-26 pubmed publisher..Collectively, our findings reveal a critical role for the PD-1/PD-L costimulatory pathway in the alphaGalCer-mediated induction of iNKT cell anergy that can be targeted for the development of immunotherapies. ..
- Yao S, Wang S, Zhu Y, Luo L, Zhu G, Flies S, et al. PD-1 on dendritic cells impedes innate immunity against bacterial infection. Blood. 2009;113:5811-8 pubmed publisher..Our results reveal a novel role of PD-1 in the negative regulation of DC function during innate immune response. ..
- RUFFNER M, Kim S, Bianco N, Francisco L, Sharpe A, Robbins P. B7-1/2, but not PD-L1/2 molecules, are required on IL-10-treated tolerogenic DC and DC-derived exosomes for in vivo function. Eur J Immunol. 2009;39:3084-90 pubmed publisher..We conclude that B7-1 and B7-2, but not PD-L1 and PD-L2, on IL-10-treated DC and DC-derived exosomes play a critical role in immunosuppressive functions of both DC and exosomes. ..
- Schreiner B, Bailey S, Shin T, Chen L, Miller S. PD-1 ligands expressed on myeloid-derived APC in the CNS regulate T-cell responses in EAE. Eur J Immunol. 2008;38:2706-17 pubmed publisher..In contrast, blockade of B7-DC has less pronounced regulatory effects. Overall, the results demonstrate that B7-H1 expressed by CNS myeloid APC negatively regulates T-cell activation during acute relapsing EAE. ..
- Frank G, Lepisto A, Freeman M, Sheridan B, Cherpes T, Hendricks R. Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of Herpes Simplex Virus 1 latency. J Immunol. 2010;184:277-86 pubmed publisher..CD4(+) T cells are not needed to maintain CD8(+) T cell memory through 34 d after infection, nor do they have a direct involvement in the maintenance of HSV-1 latency...
- Lukens J, Cruise M, Lassen M, Hahn Y. Blockade of PD-1/B7-H1 interaction restores effector CD8+ T cell responses in a hepatitis C virus core murine model. J Immunol. 2008;180:4875-84 pubmed..This also suggests that manipulation of the PD-1/B7-H1 pathway may be a potential immunotherapy to enhance effector T cell responses during persistent HCV infection. ..
- Yamazaki T, Akiba H, Koyanagi A, Azuma M, Yagita H, Okumura K. Blockade of B7-H1 on macrophages suppresses CD4+ T cell proliferation by augmenting IFN-gamma-induced nitric oxide production. J Immunol. 2005;175:1586-92 pubmed
- Zozulya A, Ortler S, Fabry Z, Sandor M, Wiendl H. The level of B7 homologue 1 expression on brain DC is decisive for CD8 Treg cell recruitment into the CNS during EAE. Eur J Immunol. 2009;39:1536-43 pubmed publisher..The recruitment of regulatory-type CD8(+) T cells into the CNS and the role of brain DC expressing B7-homologue 1 molecules in this process open up the possibility of DC-targeted therapeutic manipulation of neuroinflammatory diseases. ..
- Blackburn S, Shin H, Freeman G, Wherry E. Selective expansion of a subset of exhausted CD8 T cells by alphaPD-L1 blockade. Proc Natl Acad Sci U S A. 2008;105:15016-21 pubmed publisher..These results have implications for predicting clinical responses to PD-1-based therapeutic interventions and for understanding T cell dynamics during persisting infections. ..
- Liang S, Greenwald R, Latchman Y, Rosas L, Satoskar A, Freeman G, et al. PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis. Eur J Immunol. 2006;36:58-64 pubmed..Taken together, our results demonstrate that PD-L1 and PD-L2 have distinct roles in regulating the immune response to L. mexicana. ..
- Ishida M, Iwai Y, Tanaka Y, Okazaki T, Freeman G, Minato N, et al. Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues. Immunol Lett. 2002;84:57-62 pubmed..Thus, present results demonstrate the distinct expression patterns of PD-L1 and PD-L2 with the cells of lymphohematopoietic tissues exclusively expressing the former. ..
- Barber D, Wherry E, Masopust D, Zhu B, Allison J, Sharpe A, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439:682-7 pubmed..These studies identify a specific mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections. ..
- Erickson J, Gilchuk P, Hastings A, Tollefson S, Johnson M, Downing M, et al. Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J Clin Invest. 2012;122:2967-82 pubmed publisher..Therefore, the PD-1/PD-L1 pathway may represent a therapeutic target in the treatment of respiratory viruses...
- Hori J, Wang M, Miyashita M, Tanemoto K, Takahashi H, Takemori T, et al. B7-H1-induced apoptosis as a mechanism of immune privilege of corneal allografts. J Immunol. 2006;177:5928-35 pubmed..B7-H1 expressed on corneal endothelial cells maintains long-term acceptance of the corneal allografts by inducing apoptosis of effector T cells within the cornea. ..
- Phares T, Ramakrishna C, Parra G, Epstein A, Chen L, Atkinson R, et al. Target-dependent B7-H1 regulation contributes to clearance of central nervous system infection and dampens morbidity. J Immunol. 2009;182:5430-8 pubmed publisher..However, the beneficial role of PD-1:B7-H1 interactions in limiting morbidity highlights the need to evaluate tissue-specific intervention strategies...
- Freeman G, Long A, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027-34 pubmed..PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation. ..
- Lazar Molnar E, Gacser A, Freeman G, Almo S, Nathenson S, Nosanchuk J. The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum. Proc Natl Acad Sci U S A. 2008;105:2658-63 pubmed publisher..The results show that the PD-1/PD-L pathway has a key role in the regulation of antifungal immunity, and suggest that manipulation of this pathway represents a strategy of immunotherapy for histoplasmosis. ..
- Ito T, Ueno T, Clarkson M, Yuan X, Jurewicz M, Yagita H, et al. Analysis of the role of negative T cell costimulatory pathways in CD4 and CD8 T cell-mediated alloimmune responses in vivo. J Immunol. 2005;174:6648-56 pubmed..Harnessing physiological mechanisms that regulate alloimmunity should lead to development of novel strategies to induce durable and reproducible transplantation tolerance. ..
- Yi T, Li X, Yao S, Wang L, Chen Y, Zhao D, et al. Host APCs augment in vivo expansion of donor natural regulatory T cells via B7H1/B7.1 in allogeneic recipients. J Immunol. 2011;186:2739-49 pubmed publisher..and exacerbation of graft-versus-host disease, which was associated with downregulation of host APC expression of B7H1. Furthermore, host APC expression of B7H1 was shown to augment donor Treg survival and expansion...
- Schilbach K, Schick J, Wehrmann M, Wollny G, Simon P, Perikles S, et al. PD-1-PD-L1 pathway is involved in suppressing alloreactivity of heart infiltrating t cells during murine gvhd across minor histocompatibility antigen barriers. Transplantation. 2007;84:214-22 pubmed..Further studies are needed to refine the significance of the PD-L1 pathway in GVHD and its versatility for therapeutic intervention. ..
- Tanaka K, Albin M, Yuan X, Yamaura K, Habicht A, Murayama T, et al. PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection. J Immunol. 2007;179:5204-10 pubmed..Early as well as delayed blockade of PDL1 but not PDL2 abrogated tolerance induced by CTLA4Ig in a fully MHC-mismatched cardiac allograft model...
- Yi T, Chen Y, Wang L, Du G, Huang D, Zhao D, et al. Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease. Blood. 2009;114:3101-12 pubmed publisher..These results indicate donor CD4(+) T cells can reciprocally differentiate into Th1, Th2, and Th17 cells that mediate organ-specific GVHD. ..
- Augello A, Tasso R, Negrini S, Amateis A, Indiveri F, Cancedda R, et al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol. 2005;35:1482-90 pubmed..Taken together, these results highlight the complexity of the role of BMSC in regulating the immune response, asserting the possibility of their therapeutic application in transplantation and autoimmune diseases. ..
- Latchman Y, Wood C, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2:261-8 pubmed..Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses. ..
- Jun H, Seo S, Jeong H, Seo H, Zhu G, Chen L, et al. B7-H1 (CD274) inhibits the development of herpetic stromal keratitis (HSK). FEBS Lett. 2005;579:6259-64 pubmedThe co-signaling molecule B7-H1 (CD274) functions as both a co-inhibitor through programmed death-1 (PD-1) receptor and a co-stimulator via an as-yet-unidentified receptor on T cells...
- Park J, Omiya R, Matsumura Y, Sakoda Y, Kuramasu A, Augustine M, et al. B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood. 2010;116:1291-8 pubmed publisher..Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance. ..
- Kleinschnitz C, Schwab N, Kraft P, Hagedorn I, Dreykluft A, Schwarz T, et al. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood. 2010;115:3835-42 pubmed publisher..Our data demonstrate that T cells critically contribute to cerebral ischemia, but their detrimental effect neither depends on antigen recognition nor TCR costimulation or thrombus formation. ..
- Fife B, Pauken K, Eagar T, Obu T, Wu J, Tang Q, et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol. 2009;10:1185-92 pubmed publisher..Blockade of the immunomodulatory receptor CTLA-4 did not alter T cell motility or abrogate tolerance. Thus, PD-1-PD-L1 interactions maintain peripheral tolerance by mechanisms fundamentally distinct from those of CTLA-4...
- Wang S, Bajorath J, Flies D, Dong H, Honjo T, Chen L. Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction. J Exp Med. 2003;197:1083-91 pubmed..Our results reveal unique binding characteristics of B7-H1 and B7-DC and provide direct evidence for an independent costimulatory receptor other than PD-1. ..
- Li W, Wang X, Chen R, Zhu H, Chen G, Sun X. Overexpression of programmed death ligand 1 in dendritic cells inhibits allogeneic lymphocyte activation in mice. J Surg Res. 2012;176:e79-87 pubmed publisher..05). PD-L1 delivers an immunoinhibitory signal, suppressing T cell activation. Overexpression of PD-L1 signaling induces tolerance, which presents a promising immunotherapeutic approach for long-term graft acceptance. ..
- Chang W, Kim J, Kim Y, Kim Y, Lee J, Azuma M, et al. Cutting edge: Programmed death-1/programmed death ligand 1 interaction regulates the induction and maintenance of invariant NKT cell anergy. J Immunol. 2008;181:6707-10 pubmed..Our findings suggest that the PD-1/PD-L1 interaction is essential for the induction and maintenance of iNKT cell anergy. ..
- Magnus T, Schreiner B, Korn T, Jack C, Guo H, Antel J, et al. Microglial expression of the B7 family member B7 homolog 1 confers strong immune inhibition: implications for immune responses and autoimmunity in the CNS. J Neurosci. 2005;25:2537-46 pubmed..Human and mouse microglial cells constitutively express B7 homolog 1 (B7-H1) in vitro...
- Carter L, Leach M, Azoitei M, Cui J, Pelker J, Jussif J, et al. PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2007;182:124-34 pubmed..These results demonstrate that interactions between PD-1/PD-L1, but not PD-1/PDL-2, are crucial in attenuating T cell responses in EAE. ..
- Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 2002;169:5538-45 pubmed..The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation...
- Keir M, Liang S, Guleria I, Latchman Y, Qipo A, Albacker L, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203:883-95 pubmed..These data provide evidence that PD-L1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1-PD-L1 interactions in mediating tissue tolerance. ..
- Smith P, Walsh C, Mangan N, Fallon R, Sayers J, McKenzie A, et al. Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages. J Immunol. 2004;173:1240-8 pubmed..mansoni worms have usurped the natural function of PD-L1 to reduce T cell activation during early acute stages of infection before the subsequent emergence of egg-induced T cell suppression in the chronic stages of infection. ..
- Klotz L, Hucke S, Thimm D, Classen S, Gaarz A, Schultze J, et al. Increased antigen cross-presentation but impaired cross-priming after activation of peroxisome proliferator-activated receptor gamma is mediated by up-regulation of B7H1. J Immunol. 2009;183:129-36 pubmed publisher..Concomitantly, activation of PPARgamma in dendritic cells induced up-regulation of the coinhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8(+) T cells and ..
- Grabie N, Gotsman I, Dacosta R, Pang H, Stavrakis G, Butte M, et al. Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart. Circulation. 2007;116:2062-71 pubmed..Myocardial PD-L1, mainly localized on endothelium, is critical for control of immune-mediated cardiac injury and polymorphonuclear leukocyte inflammation. ..
- Rajasalu T, Brosi H, Schuster C, Spyrantis A, Boehm B, Chen L, et al. Deficiency in B7-H1 (PD-L1)/PD-1 coinhibition triggers pancreatic beta-cell destruction by insulin-specific, murine CD8 T-cells. Diabetes. 2010;59:1966-73 pubmed publisher..Hence, regulation of the susceptibility of the beta-cells for a preproinsulin-specific CD8 T-cell attack can allow or suppress EAD. ..
- Tamura H, Dong H, Zhu G, Sica G, Flies D, Tamada K, et al. B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. Blood. 2001;97:1809-16 pubmed..The study thus identifies a unique costimulatory pathway that preferentially affects T-helper cell functions. ..
- Lafon M, Mégret F, Meuth S, Simon O, Velandia Romero M, Lafage M, et al. Detrimental contribution of the immuno-inhibitor B7-H1 to rabies virus encephalitis. J Immunol. 2008;180:7506-15 pubmed..They show that the B7-H1/PD-1 pathway can be exploited locally and in an organ specific manner--here the nervous system--by a neurotropic virus to promote successful host invasion. ..
- Eppihimer M, Gunn J, Freeman G, Greenfield E, Chernova T, Erickson J, et al. Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation. 2002;9:133-45 pubmed..These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-alpha, -beta, and -gamma, and suggest a potential pathway by which ECs may modulate T-cell function. ..
- Lee S, O Donnell H, McSorley S. B7-H1 (programmed cell death ligand 1) is required for the development of multifunctional Th1 cells and immunity to primary, but not secondary, Salmonella infection. J Immunol. 2010;185:2442-9 pubmed publisher..Together, these data demonstrate that B7-H1 is required for the generation of multifunctional Th1 responses and optimal protective immunity to primary Salmonella infection. ..
- Ortler S, Leder C, Mittelbronn M, Zozulya A, Knolle P, Chen L, et al. B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage: implications for the lesion pathogenesis of multiple sclerosis. Eur J Immunol. 2008;38:1734-44 pubmed publisher..Our findings demonstrate the critical importance of B7-H1 as an immune-inhibitory molecule capable of down-regulating T cell responses thus contributing to the confinement of immunopathological damage. ..
- Mueller S, Vanguri V, Ha S, West E, Keir M, Glickman J, et al. PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice. J Clin Invest. 2010;120:2508-15 pubmed publisher..Together, these data demonstrate that there are distinct roles for PD-L1 on hematopoietic and nonhematopoietic cells in regulating CD8+ T cell responses and viral clearance during chronic viral infection. ..
- Francisco L, Salinas V, Brown K, Vanguri V, Freeman G, Kuchroo V, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206:3015-29 pubmed publisher..These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity. ..
- Butte M, Keir M, Phamduy T, Sharpe A, Freeman G. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27:111-22 pubmed..Our findings point to a substantial bidirectional inhibitory interaction between B7-1 and PD-L1 and add an additional dimension to immunoregulatory functions of the B7:CD28 family. ..
- Barber D, Mayer Barber K, Feng C, Sharpe A, Sher A. CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition. J Immunol. 2011;186:1598-607 pubmed publisher..Thus, in the absence of the PD-1 pathway, M. tuberculosis benefits from CD4 T cell responses, and host resistance requires inhibition by PD-1 to prevent T cell-driven exacerbation of the infection. ..
- Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99:12293-7 pubmed
- Guleria I, Gubbels Bupp M, Dada S, Fife B, Tang Q, Ansari M, et al. Mechanisms of PDL1-mediated regulation of autoimmune diabetes. Clin Immunol. 2007;125:16-25 pubmedThe PD-1-PDL1 pathway plays a critical role in regulating autoimmune diabetes as blockade or deficiency of PD-1 or PDL1 results in accelerated disease in NOD mice...
- Latchman Y, Liang S, Wu Y, Chernova T, Sobel R, Klemm M, et al. PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells. Proc Natl Acad Sci U S A. 2004;101:10691-6 pubmed..These results demonstrate that PD-L1 on T cells, APCs, and host tissue inhibits naïve and effector T cell responses and plays a critical role in T cell tolerance. ..
- Subudhi S, Zhou P, Yerian L, Chin R, Lo J, Anders R, et al. Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection. J Clin Invest. 2004;113:694-700 pubmed..Ig fusion protein augmented naive T cell priming both in vitro and in vivo. Our results demonstrate that B7-H1 can provide positive costimulation for naive T cells to promote allograft rejection and autoimmune disease pathogenesis. ..
- Akbari O, Stock P, Singh A, Lombardi V, Lee W, Freeman G, et al. PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway hyperreactivity in opposing directions. Mucosal Immunol. 2010;3:81-91 pubmed publisher..These studies also indicate that PD-L1 and PD-L2 have important but opposing roles in the regulation of AHR and iNKT-cell-mediated activation. ..
- Dong H, Zhu G, Tamada K, Flies D, van Deursen J, Chen L. B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity. 2004;20:327-36 pubmed..Therefore, B7-H1 is a key protein selectively regulating the accumulation and deletion of intrahepatic CD8(+) T cells and may also contribute to inflammation, autoimmune diseases, and tolerance in the liver. ..
- Allen S, Hamrah P, Gate D, Mott K, Mantopoulos D, Zheng L, et al. The role of LAT in increased CD8+ T cell exhaustion in trigeminal ganglia of mice latently infected with herpes simplex virus 1. J Virol. 2011;85:4184-97 pubmed publisher..Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8(+) T cell exhaustion and latency in HSV-1 infection. ..
- Guleria I, Khosroshahi A, Ansari M, Habicht A, Azuma M, Yagita H, et al. A critical role for the programmed death ligand 1 in fetomaternal tolerance. J Exp Med. 2005;202:231-7 pubmed..Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model...
- Carter L, Fouser L, Jussif J, Fitz L, Deng B, Wood C, et al. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol. 2002;32:634-43 pubmed..However, CD8(+) T cells may be more sensitive to modulation by the PD-1:PD-L pathway because of their intrinsic inability to produce significant levels of IL-2. ..
- Tsushima F, Iwai H, Otsuki N, Abe M, Hirose S, Yamazaki T, et al. Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses. Eur J Immunol. 2003;33:2773-82 pubmed..Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses. ..