Interleukin-2 gene deletion produces a robust reduction in susceptibility to experimental autoimmune encephalomyelitis in C57BL/6 mice.
Dysregulation of interleukin-2 (IL-2), the prototypical T cell growth factor and immunoregulatory cytokine, may modify self-tolerance and predisposition to autoimmunity. The available literature suggested that IL-2 could be hypothesized to either propagate or inhibit the development autoimmune demyelinating disorders of the central nervous system such as multiple sclerosis. Thus, the present study sought to test these competing hypotheses by examining whether disrupting one or both IL-2 gene alleles would render mice more or less vulnerable to experimental autoimmune encephalomyelitis (EAE). Myelin oligodendrocyte glycoprotein was used to induce EAE in C57BL/6-IL-2(-/-) knockout, C57BL/6-IL-2(+/-) heterozygote and C57BL/6-IL-2(+/+) wild-type mice. All of the wild-type and heterozygote mice developed signs of EAE compared with only 23% of the IL-2 knockout mice. Histopathological examination of lumbar spinal cord sections confirmed that subpial perivascular inflammatory infiltrates found in wild-type and heterozygote mice were absent in the unaffected IL-2 knockout mice. These data demonstrate that vulnerability to EAE is markedly reduced in C57BL/6 mice lacking IL-2, and suggest that this cytokine may play a critical role in autoimmune processes of the central nervous system.
Petitto
J M
JM
Department of Psychiatry, UF Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610-0256, USA. jpetitto@psych.med.ufl.edu
Streit
W J
WJ
Huang
Z
Z
Butfiloski
E
E
Schiffenbauer
J
J
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000517:prevention & control*; D005260:Female; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000517:prevention & control*; D006720:Homozygote; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D007376:Interleukin-2