Aggravated experimental autoimmune encephalomyelitis in IL-15 knockout mice.
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.
Gomez-Nicola
Diego
D
Neural Plasticity Group, Functional and Systems Neurobiology Department, Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
Spagnolo
Alessandra
A
Guaza
Carmen
C
Nieto-Sampedro
Manuel
M
D000704:Analysis of Variance; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology; D004609:Eliminative Behavior, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006023:Glycoproteins; D019409:Interleukin-15 / Q000172:deficiency*; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D020556:Neutrophil Infiltration / Q000276:immunology; D010446:Peptide Fragments; D019707:Receptors, Chemokine / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000503:physiopathology
D015704:CD4 Antigens; D016827:CD8 Antigens; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D006023:Glycoproteins; D019409:Interleukin-15; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019707:Receptors, Chemokine; C445081:myelin oligodendrocyte glycoprotein (35-55)