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Glatiramer acetate (Copaxone) inhibits natural killer cells lysis of tumor cells but enhances their killing of autologous and allogeneic immature and mature dendritic cells.
Author(s) -
Maghazachi Azzam A,
Sand Kristin L,
Becerra Cecilia B,
Rolin Johannes,
Knudsen Eirunn
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.465
Subject(s) - nkg2d , glatiramer acetate , cd80 , cd86 , cd16 , interleukin 12 , natural killer cell , dendritic cell , lymphokine activated killer cell , chemistry , microbiology and biotechnology , cytolysis , cd14 , immunology , biology , interleukin 21 , cancer research , cytotoxic t cell , flow cytometry , immune system , t cell , cd40 , in vitro , multiple sclerosis , cd8 , biochemistry , cd3
We describe a new mechanism of action for the drug Glatiramer acetate (GA; Copaxone). GA ameliorated experimental autoimmune encephalomyelitis (EAE) in SJL mice corroborating with complete inhibition of NK cells cytolysis of mouse tumor target cells. In contrast, GA did not affect NK cells number or the expression of CD69 activation molecule after dosing EAE mice with GA. Further analysis showed that incubating GA with the mixtures of human NK cells and tumor cells inhibited the lytic activity of the cytolytic CD16 + CD56 −/low and IL‐2‐activated NK cell subsets. However, GA did not affect the proliferation of CD16 + CD56 −/low , CD16 − CD56 +/high or IL‐2‐activated NK cellsand neither affected the expression of CD69 molecule on the surfaces of these cells. Surprisingly, GA enhanced the cytolysis of IL‐2‐activated NK cells against autologous and allogeneic immature and mature monocyte‐derived dendritic cells (DCs). GA down‐regulated the expression of CD83 and HLA‐DR in mature DCs but did not affect the surface expression of CD80, CD86, HLA‐I, or CCR7 on immature or mature monocyte‐derived DCs. Neither has GA affected the surface expression of NKG2D, NKp30, or NKp44 on IL‐2‐activated NK cells. Anti‐NKp30 and anti‐CD86 inhibited GA activity for immature DCs but not mDCs, suggesting that the mechanism of NK cell killing induced by GA is different among the two cell types. These findings may have important implications for the treatment of autoimmune diseases such as multiple sclerosis, as well as in allograft rejection.