Abstract Details

Title Glatiramer Acetate Does Not Interfere with CNS Immune Surveillance in an Animal Model of Toxoplasmosis Gondii Infection

Topic Infections/AIDS/Prion Disease

Presentation(s) P04 - (-)

Poster/Presentation
Number 011

Objective

Background BACKGROUND: Infection of C57BL/6 mice with T. gondii strain ME49 infection causes an acute infection characterized by an expansion of tachyzoites. Following the acute phase, tachyzoites differentiate into bradyzoites, which form tissue cysts predominantly in the CNS. The development of tissue cysts defines the chronic stage of the infection. Interventions that interfere with the innate or adaptive arm of the immune system adversely affect the lifespan of the host.

Design/Methods DESIGN/METHODS: We infected groups of 10 eight week old female C57BL/6 mice i.p. with 20 cysts per mouse of the avirulent type II T. gondii strain ME49. Recipients were left untreated, treated daily with subcutaneous injections of 150 [micro]g of GA6, oral FTY720 (0.3 mg/kg/day)7, or both for another 50 days. Mice were monitored for survival. T. gondii cysts in the brain and spinal cord were quantified as described above. The frequency and phenotype of immunocompetent cells in the CNS were assessed by multi-parameter flow cytometry.

Results RESULTS: Neither treatment group had an adverse effect on host survival. Compared to untreated mice, the number of paracytes in the brains of GA-treated animals was not increased. In contrast, the number of paracyte cysts more than doubled in FTY720-treated animals. Interestingly, addition of GA to FTY720 reduced the number of brain cysts back to baseline. Both GA treatment paradigms were associated with an expansion of CD8+ T cells in the brain.

Conclusions CONCLUSIONS: T. gondii infection of C57BL/6 mice presents a valid model of CNS immunesurveillance for MS pharmacotherapies. GA is a safe agent that does not alter survival of experimental animals, and that does not promote expansion of paracyte cysts in the brain.

Authors/Disclosures
PRESENTER	No disclosure on file
Liat Hayardeny Nisimov, PhD (Teva)	No disclosure on file
	No disclosure on file
	No disclosure on file
Olaf Stuve, MD, PhD, FAAN (UT Southwestern Medical Center)	Dr. Stuve has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Stuve has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Stuve has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Therapeutic Advances in Neurological Diseases. Dr. Stuve has received research support from US Department of Veterans Affairs. Dr. Stuve has received research support from National Multiple Sclerosis Society (US). Dr. Stuve has received research support from Merck KGaA.
Per Soelberg Sorensen	No disclosure on file

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