title: Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate.
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-gamma 24 h but increased the release of TNF-alpha 48 h after incubation with NK cells.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: K L
authors.initials: KL
authors.lastname: Sand
authors.forename: E
authors.initials: E
authors.lastname: Knudsen
authors.forename: J
authors.initials: J
authors.lastname: Rolin
authors.forename: Y
authors.initials: Y
authors.lastname: Al-Falahi
authors.forename: A A
authors.initials: AA
authors.lastname: Maghazachi
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003713:Dendritic Cells; D000068717:Glatiramer Acetate; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D010455:Peptides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D000068717:Glatiramer Acetate; D007371:Interferon-gamma