Open AccessSplenic natural killer cell activity in two models of experimental neurodegenerative diseases
Author(s) -
AlFalahi Yassin,
Sand Kristin L.,
Knudsen Eirunn,
Damaj Bassam B.,
Rolin Johannes,
Maghazachi Azzam A.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00640.x
Subject(s) - biology , immunology , experimental autoimmune encephalomyelitis , spleen , natural killer cell , natural killer t cell , immune system , interleukin 12 , microbiology and biotechnology , cytotoxic t cell , t cell , in vitro , biochemistry
Natural killer (NK) cells are antitumour/anti‐viral effectors and play important roles in shaping the immune system, but their role in neurodegenerative diseases is not clear. Here, we investigated the fate of these cells in two neurodegenerative diseases. In the first model, the activity of NK cells was examined in mice with experimental autoimmune encephalomyelitis (EAE) treated with glatiramer acetate (GA or Copaxone), a drug used to treat EAE in animals and multiple sclerosis in human. The second disease model is twitcher ( Galc twi / Galc twi ) mice, which represents an authentic model of human Krabbe’s disease. Administration of GA ameliorated EAE in SJL mice corroborated with isolating NK cells that expressed higher killing than cells isolated from vehicle‐dosed animals against immature or mature dendritic cells (DCs). However, this drug showed no effect on the numbers of NK cells or the expression of CD69 molecule. On the other hand, NK cells either disappeared from the spleens or were present in low numbers in the white pulp areas of Galc twi / Galc twi mice, which have increased D‐galactosyl‐β1–1′‐sphingosine (GalSph) levels. Analysis by confocal microscopy shows that NK cells found in the spleens of Galc twi / Galc twi mice were apoptotic. Incubating NK cells in vitro with GalSph induced the apoptosis in these cells, confirming the results of twitcher mice. Our results provide the first evidence showing that amelioration of EAE in mice is corroborated with NK cell lysis of antigen‐presenting DCs, whereas NK cell distribution into the spleen is altered in a devastating lipid disorder corroborated with induction of their apoptosis.