Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate |
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Authors: | K L Sand E Knudsen J Rolin Y Al-Falahi A A Maghazachi |
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Institution: | (1) Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway |
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Abstract: | Glatiramer acetate (GA or Copaxone) is a drug used to treat experimental autoimmune encephalomyelitis in mice and multiple
sclerosis in human. Here, we describe a new mechanism of action for this drug. GA enhanced the cytolysis of human NK cells
against autologous and allogeneic immature and mature monocyte-derived dendritic cells (DCs). This drug reduced the percentages
of mature DCs expressing CD80, CD83, HLA-DR or HLA-I. In contrast, it did not modulate the percentages of NK cells expressing
NKG2D, NKp30, or NKp44. Nonetheless, anti-NKp30 or anti-CD86 inhibited GA-enhanced human NK cell lysis of immature DCs. Hence,
CD86, and NKp30 are important for NK cell lysis of immature DCs, whereas CD80, CD83, HLA-DR and HLA-I are important for the
lysis of mature DCs when GA is used as a stimulus. Further, GA inhibited the release of IFN-γ 24 h but increased the release
of TNF-α 48 h after incubation with NK cells.
Received 13 November 2008; received after revision 10 February 2009; accepted 18 February 2009 |
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Keywords: | " target="_blank"> Glatiramer acetate NK cells dendritic cells cytotoxicity autoimmunity |
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