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Gene Review

Cd274  -  CD274 antigen

Mus musculus

Synonyms: A530045L16Rik, B7 homolog 1, B7-H1, B7h1, PD-L1, ...
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Disease relevance of Cd274


High impact information on Cd274

  • Remarkably, blocking the interaction between PD-1 and its ligand, PD-L1, reactivates these T cells and reduces viral load [7].
  • Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B7-H1, a member of the B7 family, on the cell surface [8].
  • Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B7-H1 [8].
  • T cells conditioned with the B7-H1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice [8].
  • Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion [9].

Chemical compound and disease context of Cd274

  • Streptozotocin-induced diabetic SCID mice implanted with PDL-induced cell aggregates were able to maintain glucose concentrations below 200 mg/dL for over 70 days (n = 5) [10].

Biological context of Cd274


Anatomical context of Cd274


Associations of Cd274 with chemical compounds


Regulatory relationships of Cd274


Other interactions of Cd274

  • 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 [1].
  • Flow cytometry on in vivo and in vitro worm-modulated Mphi revealed that of the family of B7 costimulatory molecules, only programmed death ligand 1 (PD-L1) was selectively up-regulated [13].
  • Exogenous IL-2 is able to overcome PD-L1-mediated inhibition at all times, indicating that cells maintain IL-2 responsiveness [25].
  • Paradoxically, it has been reported that both B7-H1 and B7-DC co-stimulate or inhibit T cell proliferation and cytokine production [24].
  • In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis [26].

Analytical, diagnostic and therapeutic context of Cd274

  • In initial studies, we found that most normal tissues and cardiac isografts had minimal expression of PD-1, PD-L1, or PD-L2, but intragraft induction of all three molecules occurred during development of cardiac allograft rejection [27].
  • RT-PCR and real-time PCR revealed that both PD-L1 and PD-L2 genes were expressed in tumor and vicinal muscle tissues of tumor-bearing mice and the expression level was significantly increased if a higher dosage of pSLC was administered [28].
  • Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy [3].
  • Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load [29].
  • However, concurrent administration of anti-PD-1 or anti-PD-L1 mAb abrogated prolonged survival after the adoptive transfer (MST, 14 and 20 days, respectively) [30].


  1. Differential role of programmed death-ligand 1 and programmed death-ligand 2 in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis. Zhu, B., Guleria, I., Khosroshahi, A., Chitnis, T., Imitola, J., Azuma, M., Yagita, H., Sayegh, M.H., Khoury, S.J. J. Immunol. (2006) [Pubmed]
  2. Blockade of B7-H1 suppresses the development of chronic intestinal inflammation. Kanai, T., Totsuka, T., Uraushihara, K., Makita, S., Nakamura, T., Koganei, K., Fukushima, T., Akiba, H., Yagita, H., Okumura, K., Machida, U., Iwai, H., Azuma, M., Chen, L., Watanabe, M. J. Immunol. (2003) [Pubmed]
  3. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Blank, C., Gajewski, T.F., Mackensen, A. Cancer Immunol. Immunother. (2005) [Pubmed]
  4. Tissue expression of PD-L1 mediates peripheral T cell tolerance. Keir, M.E., Liang, S.C., Guleria, I., Latchman, Y.E., Qipo, A., Albacker, L.A., Koulmanda, M., Freeman, G.J., Sayegh, M.H., Sharpe, A.H. J. Exp. Med. (2006) [Pubmed]
  5. HSP70 vaccine in combination with gene therapy with plasmid DNA encoding sPD-1 overcomes immune resistance and suppresses the progression of pulmonary metastatic melanoma. Geng, H., Zhang, G.M., Xiao, H., Yuan, Y., Li, D., Zhang, H., Qiu, H., He, Y.F., Feng, Z.H. Int. J. Cancer (2006) [Pubmed]
  6. Programmed death 1 ligand (PD-L) 1 and PD-L2 limit autoimmune kidney disease: distinct roles. Menke, J., Lucas, J.A., Zeller, G.C., Keir, M.E., Huang, X.R., Tsuboi, N., Mayadas, T.N., Lan, H.Y., Sharpe, A.H., Kelley, V.R. J. Immunol. (2007) [Pubmed]
  7. Rejuvenating exhausted T cells during chronic viral infection. Okazaki, T., Honjo, T. Cell (2006) [Pubmed]
  8. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Curiel, T.J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K.L., Daniel, B., Zimmermann, M.C., David, O., Burow, M., Gordon, A., Dhurandhar, N., Myers, L., Berggren, R., Hemminki, A., Alvarez, R.D., Emilie, D., Curiel, D.T., Chen, L., Zou, W. Nat. Med. (2003) [Pubmed]
  9. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Dong, H., Strome, S.E., Salomao, D.R., Tamura, H., Hirano, F., Flies, D.B., Roche, P.C., Lu, J., Zhu, G., Tamada, K., Lennon, V.A., Celis, E., Chen, L. Nat. Med. (2002) [Pubmed]
  10. Long-term correction of hyperglycemia in diabetic mice after implantation of cultured human cells derived from fetal pancreas. Wu, F., Jagir, M., Powell, J.S. Pancreas (2004) [Pubmed]
  11. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. Freeman, G.J., Long, A.J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L.J., Malenkovich, N., Okazaki, T., Byrne, M.C., Horton, H.F., Fouser, L., Carter, L., Ling, V., Bowman, M.R., Carreno, B.M., Collins, M., Wood, C.R., Honjo, T. J. Exp. Med. (2000) [Pubmed]
  12. B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. Tamura, H., Dong, H., Zhu, G., Sica, G.L., Flies, D.B., Tamada, K., Chen, L. Blood (2001) [Pubmed]
  13. Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages. Smith, P., Walsh, C.M., Mangan, N.E., Fallon, R.E., Sayers, J.R., McKenzie, A.N., Fallon, P.G. J. Immunol. (2004) [Pubmed]
  14. Microglial expression of the B7 family member B7 homolog 1 confers strong immune inhibition: implications for immune responses and autoimmunity in the CNS. Magnus, T., Schreiner, B., Korn, T., Jack, C., Guo, H., Antel, J., Ifergan, I., Chen, L., Bischof, F., Bar-Or, A., Wiendl, H. J. Neurosci. (2005) [Pubmed]
  15. Expression of B7-H1 in inflammatory renal tubular epithelial cells. Chen, Y., Zhang, J., Li, J., Zou, L., Zhao, T., Tang, Y., Wu, Y. Nephron Exp. Nephrol. (2006) [Pubmed]
  16. B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism. Matsumoto, K., Inoue, H., Nakano, T., Tsuda, M., Yoshiura, Y., Fukuyama, S., Tsushima, F., Hoshino, T., Aizawa, H., Akiba, H., Pardoll, D., Hara, N., Yagita, H., Azuma, M., Nakanishi, Y. J. Immunol. (2004) [Pubmed]
  17. Expression of programmed death 1 ligands by murine T cells and APC. Yamazaki, T., Akiba, H., Iwai, H., Matsuda, H., Aoki, M., Tanno, Y., Shin, T., Tsuchiya, H., Pardoll, D.M., Okumura, K., Azuma, M., Yagita, H. J. Immunol. (2002) [Pubmed]
  18. PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells. Loke, P., Allison, J.P. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. Blockade of B7-H1 with sPD-1 improves immunity against murine hepatocarcinoma. He, L., Zhang, G., He, Y., Zhu, H., Zhang, H., Feng, Z. Anticancer Res. (2005) [Pubmed]
  20. Blockade of the interaction between PD-1 and PD-L1 accelerates graft arterial disease in cardiac allografts. Koga, N., Suzuki, J., Kosuge, H., Haraguchi, G., Onai, Y., Futamatsu, H., Maejima, Y., Gotoh, R., Saiki, H., Tsushima, F., Azuma, M., Isobe, M. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  21. Integration of topographical and biochemical cues by axons during growth on microfabricated 3-D substrates. Li, N., Folch, A. Exp. Cell Res. (2005) [Pubmed]
  22. Polylysine-functionalised thermoresponsive chitosan hydrogel for neural tissue engineering. Crompton, K.E., Goud, J.D., Bellamkonda, R.V., Gengenbach, T.R., Finkelstein, D.I., Horne, M.K., Forsythe, J.S. Biomaterials (2007) [Pubmed]
  23. Interaction of B7RP-1 with ICOS negatively regulates antigen presentation by B cells. Wahl, P., Schoop, R., Horan, T.P., Yoshinaga, S.K., Wüthrich, R.P. Inflammation (2003) [Pubmed]
  24. Blockade of B7-H1 on macrophages suppresses CD4+ T cell proliferation by augmenting IFN-gamma-induced nitric oxide production. Yamazaki, T., Akiba, H., Koyanagi, A., Azuma, M., Yagita, H., Okumura, K. J. Immunol. (2005) [Pubmed]
  25. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Carter, L., Fouser, L.A., Jussif, J., Fitz, L., Deng, B., Wood, C.R., Collins, M., Honjo, T., Freeman, G.J., Carreno, B.M. Eur. J. Immunol. (2002) [Pubmed]
  26. In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis. Saudemont, A., Quesnel, B. Blood (2004) [Pubmed]
  27. Programmed death-1 targeting can promote allograft survival. Ozkaynak, E., Wang, L., Goodearl, A., McDonald, K., Qin, S., O'Keefe, T., Duong, T., Smith, T., Gutierrez-Ramos, J.C., Rottman, J.B., Coyle, A.J., Hancock, W.W. J. Immunol. (2002) [Pubmed]
  28. Blocking programmed death-1 ligand-PD-1 interactions by local gene therapy results in enhancement of antitumor effect of secondary lymphoid tissue chemokine. He, Y.F., Zhang, G.M., Wang, X.H., Zhang, H., Yuan, Y., Li, D., Feng, Z.H. J. Immunol. (2004) [Pubmed]
  29. Restoring function in exhausted CD8 T cells during chronic viral infection. Barber, D.L., Wherry, E.J., Masopust, D., Zhu, B., Allison, J.P., Sharpe, A.H., Freeman, G.J., Ahmed, R. Nature (2006) [Pubmed]
  30. Programmed death-1-programmed death-L1 interaction is essential for induction of regulatory cells by intratracheal delivery of alloantigen. Aramaki, O., Shirasugi, N., Takayama, T., Shimazu, M., Kitajima, M., Ikeda, Y., Azuma, M., Okumura, K., Yagita, H., Niimi, M. Transplantation (2004) [Pubmed]
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