Effects of Brain-Derived IL-2 Deficiency and the Development of Autoimmunity on Spatial Learning and Fear Conditioning

Interleukin-2 (IL-2) has been implicated in neurological disorders including multiple sclerosis and Alzheimer’s disease. Peripheral IL-2 deficiency in gene-deleted mice results in T cell mediated autoimmunity that begins to develop slowly after weaning and progressively increases through adulthood. Loss of brain-derived IL-2 results in neurobiological and behavioral abnormalities, and may contribute to the development of CNS autoimmunity by modifying the neuroimmunological milieu of the brain. We have shown previously that IL-2 knockout (KO) mice have altered learning acquisition in the Morris water-maze. Hypothesizing that the learning acquisition deficits in IL-2KO would be associated largely with the loss of brain-derived IL-2, the present study sought to determine if these cognitive alterations are due to the loss the IL-2 gene in the brain and/or autoimmunity resulting from loss of the gene in the peripheral immune system. We found that SCID congenic mice (mice free of IL-2 deficiency induced peripheral autoimmunity) without brain IL-2 (two IL-2KO alleles) did not differ from SCID congenic mice with normal brain IL-2 (two WT IL-2 alleles); thus, contrary to our hypothesis, loss of brain-derived IL-2 did not affect learning acquisition in the water-maze. Compared to adult WT littermates (9 weeks), adul