Immune regulatory effects of FTY720 on Dendritic cells (P1.142)

Objective: To determine the immune regulatory effects of FTY720 on Dendritic cells (DCs). Background: Dendritic cells (DCs) control the activation and differentiation of myelin-specific effector T lymphocytes and regulatory T-cells. They play a pivotal role in CNS autoimmunity and inflammatory responses. DCs are the primary cells involved in T cell education and thus significantly contribute to control the T cell mediated immunity and tolerance. FTY720 is the functional analogue of Sphingosine and is the first oral treatment for relapsing remitting Multiple Sclerosis (MS). FTY720 regulates immune cell trafficking and prevents relapses in Multiple Sclerosis. We investigated immune regulatory effects of FTY720 on dendritic cells. Method: The percentages and phenotype of immune cells in longitudinal samples from MS patients were studied by FACs (flourscence activated cell staining) analysis. DCs were purified using miltenyi bead sorting and cultured overnight in the presence or absence of FTY720. Activated DCs were co-cultured with T cells to determine the effect of FTY720 treated DCs on T cell differentiation. T cell proliferation was measured by thymidine incorporation and cytokines produced by the activated cells were measured using luminex assay. Results: We found that the percentages and the absolute numbers of total T and B cells were decreased in MS patients treated with FTY720. Interestingly, we found that the percentages and the absolute numbers of myeloid DCs were increased in the peripheral blood from FTY720 treated patients. We did not find any differences in the activation and costimulatory markers expressed by DCs before and after FTY720 treatment. We found that the DCs cultured in the presence of FTY720 have tolerogenic phenotype as T cells cultured with FTY720 treated DCS have decreased proliferation and decreased cytokine production. Conclusion: FTY720 induces tolerogenic DCs that induce less inflammatory T cell responses.