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Inflammation

, Volume 37, Issue 1, pp 116–121 | Cite as

Expression of Programmed Death-1 (PD-1) on CD4+ and CD8+ T cells in Rheumatoid Arthritis

  • Shufeng Li
  • Wensheng Liao
  • Meng Chen
  • Shiying Shan
  • Yuanlin Song
  • Shuzhen Zhang
  • Haihan Song
  • Zhen Yuan
Article

Abstract

Rheumatoid arthritis (RA) is characterized by chronic inflammatory process that targets the synovial lining of diarthrodial joints. Programmed death 1 (PD-1) plays a key role in the negative regulation of the immune response. In the current study, we investigated the expression of PD-1 on peripheral CD4+ and CD8+ T cells in RA patients. Percentage of PD-1+ cells was measured by flow cytometry in 82 RA cases and 90 healthy controls. Results showed that PD-1 expression was significantly decreased in both peripheral CD4+ and CD8+ T cells in RA (p = 0.002 and p < 0.001, respectively). Similarly, serum levels of soluble PD-1 were also downregulated in RA cases. When comparing PD-1 level in RA patients with different clinical parameters, patients with positive C-reactive protein (CRP) revealed lower proportion of PD-1 on CD4+ and CD8+ T cells than those with negative CRP. Also, disease activity score of RA patients was inversely correlated with PD-1 expression on peripheral CD4+ and CD8+ T cells. These data suggested that PD-1 may act as a negative regulator in the pathogenesis and progression of RA.

KEY WORDS

programmed death-1 T cells rheumatoid arthritis 

Notes

Conflict of Interest

No competing financial interests exist.

REFERENCES

  1. 1.
    Gravallese, E.M., Y. Harada, J.T. Wang, A.H. Gorn, T.S. Thornhill, and S.R. Goldring. 1998. Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. American Journal of Pathology 152: 943–951.PubMedCentralPubMedGoogle Scholar
  2. 2.
    Itonaga, I., Y. Fujikawa, A. Sabokbar, D.W. Murray, and N.A. Athanasou. 2000. Rheumatoid arthritis synovial macrophage-osteoclast differentiation is osteoprotegerin ligand-dependent. The Journal of Pathology 192: 97–104.PubMedCrossRefGoogle Scholar
  3. 3.
    Gravallese, E.M., C. Manning, A. Tsay, A. Naito, C. Pan, E. Amento, et al. 2000. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis and Rheumatism 43: 250–258.PubMedCrossRefGoogle Scholar
  4. 4.
    Shigeyama, Y., T. Pap, P. Kunzler, B.R. Simmen, R.E. Gay, and S. Gay. 2000. Expression of osteoclast differentiation factor in rheumatoid arthritis. Arthritis and Rheumatism 43: 2523–2530.PubMedCrossRefGoogle Scholar
  5. 5.
    Gracie, J.A., R.J. Forsey, W.L. Chan, A. Gilmour, B.P. Leung, M.R. Greer, et al. 1999. A proinflammatory role for IL-18 in rheumatoid arthritis. The Journal of Clinical Investigation 104: 1393–1401.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Dong, H., G. Zhu, K. Tamada, and L. Chen. 1999. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nature Medicine 5: 1365–1369.PubMedCrossRefGoogle Scholar
  7. 7.
    Latchman, Y., C.R. Wood, T. Chernova, D. Chaudhary, M. Borde, I. Chernova, et al. 2001. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nature Immunology 2: 261–268.PubMedCrossRefGoogle Scholar
  8. 8.
    Nishimura, H., T. Okazaki, Y. Tanaka, K. Nakatani, M. Hara, A. Matsumori, et al. 2001. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291: 319–322.PubMedCrossRefGoogle Scholar
  9. 9.
    Okazaki, T., Y. Tanaka, R. Nishio, T. Mitsuiye, A. Mizoguchi, J. Wang, et al. 2003. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nature Medicine 9: 1477–1483.PubMedCrossRefGoogle Scholar
  10. 10.
    Keir, M.E., M.J. Butte, G.J. Freeman, and A.H. Sharpe. 2008. PD-1 and its ligands in tolerance and immunity. Annual Review of Immunology 26: 677–704.PubMedCrossRefGoogle Scholar
  11. 11.
    Iwai, Y., S. Terawaki, M. Ikegawa, T. Okazaki, and T. Honjo. 2003. PD-1 inhibits antiviral immunity at the effector phase in the liver. The Journal of Experimental Medicine 198: 39–50.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Jun, H., S.K. Seo, H.Y. Jeong, H.M. Seo, G. Zhu, L. Chen, and I.H. Choi. 2005. B7-H1 (CD274) inhibits the development of herpetic stromal keratitis (HSK). FEBS Letters 579: 6259–6264.PubMedCrossRefGoogle Scholar
  13. 13.
    Kong, E.K., L. Prokunina-Olsson, W.H. Wong, C.S. Lau, T.M. Chan, M. Alarcón-Riquelme, et al. 2005. A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese. Arthritis and Rheumatism 52: 1058–1062.PubMedCrossRefGoogle Scholar
  14. 14.
    Prokunina, L., L. Padyukov, A. Bennet, U. de Faire, B. Wiman, J. Prince, et al. 2004. Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis and Rheumatism 50: 1770–1773.PubMedCrossRefGoogle Scholar
  15. 15.
    Wan, B., H. Nie, A. Liu, G. Feng, D. He, R. Xu, et al. 2006. Aberrant regulation of synovial T cell activation by soluble costimulatory molecules in rheumatoid arthritis. The Journal of Immunology 177: 8844–8850.PubMedCrossRefGoogle Scholar
  16. 16.
    Kobayashi, M., S. Kawano, S. Hatachi, C. Kurimoto, T. Okazaki, Y. Iwai, et al. 2005. Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjogren's syndrome. The Journal of Rheumatology 32: 2156–2163.PubMedGoogle Scholar
  17. 17.
    Barber, D.L., E.J. Wherry, D. Masopust, B. Zhu, J.P. Allison, A.H. Sharpe, et al. 2006. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439: 682–687.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhang, Z., J.Y. Zhang, E.J. Wherry, B. Jin, B. Xu, Z.S. Zou, et al. 2008. Dynamic programmed death 1 expression by virus specific CD8 T cells correlates with the outcome of acute hepatitis B. Gastroenterology 134: 1938–1949.PubMedCrossRefGoogle Scholar
  19. 19.
    Evans, A., A. Riva, H. Cooksley, S. Phillips, S. Puranik, A. Nathwani, et al. 2008. Programmed death 1 expression during antiviral treatment of chronic hepatitis B: Impact of hepatitis B e-antigen seroconversion. Hepatology 48: 759–769.PubMedCrossRefGoogle Scholar
  20. 20.
    Xie, Z., Y. Chen, S. Zhao, Z. Yang, X. Yao, S. Guo, et al. 2009. Intrahepatic PD-1/PD-L1 up-regulation closely correlates with inflammation and virus replication in patients with chronic HBV infection. Immunological Investigations 38: 624–638.PubMedCrossRefGoogle Scholar
  21. 21.
    Chen, Y., S. Wu, G. Guo, L. Fei, S. Guo, C. Yang, et al. 2011. Programmed death (PD)-1-deficient mice are extremely sensitive to murine hepatitis virus strain-3 (MHV-3) infection. PLoS Pathogens 7: e1001347.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Li, H., C. Wang, G. Guo, C. Gao, Y. Wu, and Y. Chen. 2012. The characteristic expression of B7-associated proteins in Langerhans cell sarcoma. Acta Histochemica 114: 733–743.PubMedCrossRefGoogle Scholar
  23. 23.
    Jin, H.T., R. Ahmed, and T. Okazaki. 2011. Role of PD-1 in regulating T-cell immunity. Current Topics in Microbiology and Immunology 350: 17–37.PubMedGoogle Scholar
  24. 24.
    Francisco, L.M., P.T. Sage, and A.H. Sharpe. 2010. The PD-1 pathway in tolerance and autoimmunity. Immunology Reviews 236: 219–242.CrossRefGoogle Scholar
  25. 25.
    Shin, T., G. Kennedy, K. Gorski, H. Tsuchiya, H. Koseki, M. Azuma, et al. 2003. Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor. The Journal of Experimental Medicine 198: 31–38.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Tseng, S.Y., M. Otsuji, K. Gorski, X. Huang, J.E. Slansky, S.I. Pai, et al. 2001. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. The Journal of Experimental Medicine 193: 839–846.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Dong, H., S.E. Strome, D.R. Salomao, H. Tamura, F. Hirano, D.B. Flies, et al. 2002. Tumor-associated B7-H1 promotes T cell apoptosis: a potential mechanism of immune evasion. Nature Medicine 8: 793–800.PubMedCrossRefGoogle Scholar
  28. 28.
    Singh, A.K., P. Stock, and O. Akbari. 2011. Role of PD-L1 and PD-L2 in allergic diseases and asthma. Allergy 66: 155–162.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Watanabe, T., A. Bertoletti, and T.A. Tanoto. 2010. PD-1/PD-L1 pathway and T-cell exhaustion in chronic hepatitis virus infection. Journal of Viral Hepatitis 17: 453–458.PubMedCrossRefGoogle Scholar
  30. 30.
    del Rio, M.L., L. Buhler, C. Gibbons, J. Tian, and J.I. Rodriguez-Barbosa. 2008. PD-1/PD-L1, PD-1/PD-L2, and other co-inhibitory signaling pathways in transplantation. Transplant International 21: 1015–1028.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shufeng Li
    • 1
  • Wensheng Liao
    • 2
  • Meng Chen
    • 1
  • Shiying Shan
    • 1
  • Yuanlin Song
    • 3
  • Shuzhen Zhang
    • 3
  • Haihan Song
    • 4
  • Zhen Yuan
    • 1
  1. 1.Department of OrthopedicsShandong Qianfoshan HospitalJinanChina
  2. 2.Department of Orthopedicsthe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  3. 3.Shandong Academy of Agricultural SciencesJinanChina
  4. 4.Department of Internal Medicine, Emergency Center, Shanghai East Hospital, Tongji UniversityShanghaiChina

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