Aggravated experimental autoimmune encephalomyelitis in IL-15 knockout mice

Exp Neurol. 2010 Apr;222(2):235-42. doi: 10.1016/j.expneurol.2009.12.034. Epub 2010 Jan 11.

Abstract

IL-15 initially identified as a T proliferating cytokine has several structural and biological similarities with IL-2 and has been associated with a number of autoimmune diseases. Because of the scarcity of information available on the role of IL-15 in MS pathogenesis, we have investigated how the absence of IL-15 affected the development of experimental autoimmune encephalomyelitis, a mouse model of MS. Following immunization of IL-15(-/-) and C57BL/6 mice with MOG(35-55), we observed a more severe neurological impairment in the IL-15 knockout mice than in the wild-type group. The enhanced disease severity in IL-15(-/-) mice was associated with greater demyelination in the spinal cord, increased immune cell infiltration and inflammation. These events may be related to the higher CD4/CD8 ratio and the almost absent NK cell activity, congenital immune features of IL-15KO mice. Moreover, we found that the fractalkine receptor CX3CR1 was overexpressed in the spinal cord of IL-15(-/-) mice, mainly localized on infiltrating CD8(+) T cells. How these findings are contributing to the aggravated EAE development in IL-15 KO mice remain unclear and need to be further investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • CX3C Chemokine Receptor 1
  • Cytokines / metabolism
  • Demyelinating Diseases / etiology
  • Demyelinating Diseases / pathology
  • Eliminative Behavior, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Flow Cytometry
  • Gene Expression Regulation
  • Glycoproteins
  • Interleukin-15 / deficiency*
  • Killer Cells, Natural / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin Basic Protein / metabolism
  • Myelin-Oligodendrocyte Glycoprotein
  • Neutrophil Infiltration / immunology
  • Peptide Fragments
  • Receptors, Chemokine / metabolism
  • Spinal Cord / immunology
  • Spinal Cord / physiopathology

Substances

  • CD4 Antigens
  • CD8 Antigens
  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Cytokines
  • Glycoproteins
  • Interleukin-15
  • Myelin Basic Protein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Chemokine
  • myelin oligodendrocyte glycoprotein (35-55)