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 facto r and immunoregulatory cytokine, may modify self-tolerance and predispositi on to autoimmunity. The available literature suggested that IL-2 could be h ypothesized to either propagate or inhibit the development autoimmune demye linating disorders of the central nervous system such as multiple sclerosis . Thus, the present study sought to test these competing hypotheses by exam ining whether disrupting one or both IL-2 gene alleles would render mice mo re or less vulnerable to experimental autoimmune encephalomyelitis (EAE). M yelin oligodendrocyte glycoprotein was used to induce EAE i n C57BL/6-IL-2( -/-) knockout, C57BL/6-IL-2(+/-) heterozygote and C57BL/6-IL-2(+/+) wild-ty pe mice. All of the wild-type a nd heterozygote mice developed signs of EAE com pa red with only 23% of the IL-2 knockout mice. Histopathological exam ination of lumbar spinal cord sections confirmed that subpial perivascular inflammatory infiltrates found in wild-type and heterozygote mice were abse nt in the unaffected IL-2 knockout mice. These data demonstrate that vulner ability to EAE is markedly reduced in C57BL/6 mice lacking IL-2, and sugges t that this cytokine may play a critical role in autoimmune processes of th e central nervous system. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.