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.
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Received 13 November 2008; received after revision 10 February 2009; accepted 18 February 2009
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Sand, K.L., Knudsen, E., Rolin, J. et al. Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate. Cell. Mol. Life Sci. 66, 1446–1456 (2009). https://doi.org/10.1007/s00018-009-8726-1
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DOI: https://doi.org/10.1007/s00018-009-8726-1