Neurological Sciences

, Volume 28, Issue 3, pp 121–126

Expansion of CD56Bright natural killer cells in the peripheral blood of multiple sclerosis patients treated with interferon-beta



We studied how interferon-beta (IFN-β) treatment of relapsing-remitting multiple sclerosis (MS) affects subgroups of natural killer cells (NK cells). Following IFN-β treatment, there was an expansion of CD56Bright NK-cells in the peripheral blood of MS patients, while at the same time the proportion of CD56Dim cells was diminished. In a control group, the proportion of CD56Bright NK-cells was significantly higher in secondary lymphoid tissues compared to the peripheral blood of the same individual. Our findings confirm that CD56Bright NK-cells preferably locate within the secondary lymphoid tissues, where they may interact with T cells and thereby contribute to the control of the disease activity in MS.

Key words

Interferon-beta Multiple sclerosis NK cell 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:971–979PubMedCrossRefGoogle Scholar
  2. 2.
    Takahashi K, Aranami T, Endoh M et al (2004) The regulatory role of natural killer cells in multiple sclerosis. Brain 127:1917–1927PubMedCrossRefGoogle Scholar
  3. 3.
    Takahashi K, Miyake S, Kondo T et al (2001) Natural killer type 2 bias in remission of multiple sclerosis. J Clin Invest 107:R23–R29PubMedCrossRefGoogle Scholar
  4. 4.
    Infante-Duarte C, Weber A, Kratzschmar J et al (2005) Frequency of blood CX3CR1-positive natural killer cells correlates with disease activity in multiple sclerosis patients. FASEB J 19:1902–1904PubMedGoogle Scholar
  5. 5.
    Jacobs LD, Cookfair DL, Rudick RA et al (1996) Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 39:285–294PubMedCrossRefGoogle Scholar
  6. 6.
    Yong VW (2002) Differential mechanisms of action of interferon-beta and glatiramer acetate in MS. Neurology 59:802–808PubMedGoogle Scholar
  7. 7.
    Perini P, Wadhwa M, Buttarello M et al (2000) Effect of IFNbeta and anti-IFNbeta antibodies on NK cells in multiple sclerosis patients. J Neuroimmunol 105:91–95PubMedCrossRefGoogle Scholar
  8. 8.
    Kastrukoff LF, Morgan NG, Zecchini D et al (1998) A role for natural killer cells in the immunopathogenesis of multiple sclerosis. J Neuroimmunol 86:123–133PubMedCrossRefGoogle Scholar
  9. 9.
    Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640PubMedCrossRefGoogle Scholar
  10. 10.
    Li Z, Lim WK, Mahesh SP et al (2005) Cutting edge: in vivo blockade of human IL-2 receptor induces expansion of CD56(bright) regulatory NK cells in patients with active uveitis. J Immunol 174:5187–5191PubMedGoogle Scholar
  11. 11.
    Cooper MA, Fehniger TA, Turner SC et al (2001) Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood 97:3146–3151PubMedCrossRefGoogle Scholar
  12. 12.
    Campbell JJ, Qin S, Unutmaz D et al (2001) Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire. J Immunol 166:6477–6482PubMedGoogle Scholar
  13. 13.
    Fehniger TA, Cooper MA, Nuovo GJ et al (2003) CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood 101:3052–3057PubMedCrossRefGoogle Scholar
  14. 14.
    Bendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25:297–336PubMedCrossRefGoogle Scholar
  15. 15.
    Dalbeth N, Callan MF (2002) A subset of natural killer cells is greatly expanded within inflamed joints. Arthritis Rheum 46:1763–1772PubMedCrossRefGoogle Scholar
  16. 16.
    Bielekova B, Catalfamo M, Reichert-Scrivner S et al (2006) Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 103:5941–5946PubMedCrossRefGoogle Scholar
  17. 17.
    Flodstrom M, Shi FD, Sarvetnick N, Ljunggren HG (2002) The natural killer cell — friend or foe in autoimmune disease? Scand J Immunol 55:432–441PubMedCrossRefGoogle Scholar
  18. 18.
    Morse RH, Seguin R, McCrea EL, Antel JP (2001) NK cell-mediated lysis of autologous human oligodendrocytes. J Neuroimmunol 116:107–115PubMedCrossRefGoogle Scholar
  19. 19.
    Shi FD, Takeda K, Akira S et al (2000) IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-gamma by NK cells. J Immunol 165:3099–3104PubMedGoogle Scholar
  20. 20.
    Traugott U, Raine CS (1984) Further lymphocyte characterization in the central nervous system in multiple sclerosis. Ann N Y Acad Sci 436:163–180PubMedCrossRefGoogle Scholar
  21. 21.
    Matsumoto Y, Kohyama K, Aikawa Y et al (1998) Role of natural killer cells and TCR gamma delta T cells in acute autoimmune encephalomyelitis. Eur J Immunol 28:1681–1688PubMedCrossRefGoogle Scholar
  22. 22.
    Weber WE, Buurman WA, Vandermeeren MM et al (1987) Fine analysis of cytolytic and natural killer T lymphocytes in M. the CSF in multiple sclerosis and other neurologic diseases. Neurology 37:419–425PubMedGoogle Scholar
  23. 23.
    Zhang B, Yamamura T, Kondo T et al (1997) Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells. J Exp Med 186:1677–1687PubMedCrossRefGoogle Scholar
  24. 24.
    Smeltz RB, Wolf NA, Swanborg RH (1999) Inhibition of autoimmune T cell responses in the DA rat by bone marrow-derived NK cells in vitro: implications for autoimmunity. J Immunol 163:1390–1397PubMedGoogle Scholar
  25. 25.
    Xu W, Fazekas G, Hara H, Tabira T (2005) Mechanism of natural killer (NK) cell regulatory role in experimental autoimmune encephalomyelitis. J Neuroimmunol 163:24–30PubMedCrossRefGoogle Scholar
  26. 26.
    Huang D, Shi FD, Jung S et al (2006) The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system. FASEB J 20:896–905PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  1. 1.MediCity Research LaboratoryUniversity of TurkuTurkuFinland
  2. 2.Department of OtorhinolaryngologyUniversity of TurkuTurkuFinland
  3. 3.Department of NeurologyUniversity of TurkuTurkuFinland

Personalised recommendations