Fingolimod Effects on CD8 Cells in Multiple Sclerosis (P1.157)

OBJECTIVE: Determine effect of fingolimod/FTY720 on the CD69 activation/adhesion molecule (important for cell retention in lymph nodes) on CD8 cells (important in CNS damage and immune regulation). We hypothesized that FTY would decrease CD69 expression on CD8+CD28- cell, allowing more egress from lymph nodes. BACKGROUND: CD8+,CD28- T cells are powerful regulatory cells in MS, and CD8+,CD28+ cytotoxic cells damage CNS neurons. Fingolimod alters trafficking and migration of CD4 effector memory T cells by trapping them in lymph nodes (LN). The CD69 molecule increases CD4 cell retention in LN. DESIGN/METHODS: In 14 healthy controls and in 14 therapy-naive, relapsing MS patients, lymphocyte subsets were exposed to 10-100 ng/ml FTY agonists or antagonists, and then activated with 5 ug/ml ConA to bypass the lack of CD3/CD28 costimulatory proteins on CD28- T cells. Multiparameter flow cytometry measured membrane protein expression. RESULTS: Activation increased CD69 200-fold on CD4, CD8+CD28+ and CD8+CD28- cells at 12 hours. FTY agonists reduced CD69 expression on all subsets by 10-15[percnt]. CFSE proliferation was also equivalent in CD4+, CD8+CD28+, and CD8+CD28- subsets. CONCLUSIONS: Fingolimod reduces CD69 on CD8 cytolytic and regulatory T cells and may affect adhesion and lymph node retention of both CD8 subsets as well as CD4 cells. These data are important in monitoring immune effects and potential drug synergy of fingolimod with other agents. Study Supported by: Novartis Disclosure: Dr. Reder received personal compensation from Acorda Therapeutics, Inc., Bayer Pharmaceuticals Corporation, Biogen Idec, EMD Serono, Genzyme Corporation, Novartis, Pfizer Inc., Questcor, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience as a consultan Dr. Causevic has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Testai has nothing to disclose. Dr. Feng has nothing to disclose.