In contrast to natalizumab, fingolimod blocks egress of lymphocytes from secondary lymphoid organs (SLO) such as lymph nodes. This effect is mediated by functional antagonization sphingosine-1-phosphate (S1P) receptors on lymphocytes by fingolimod. Due to a different expression of lymph node homing receptors naïve and central memory T-cells regularly circulate to SLO and are consequently more prone to sequestration to SLO than effector memory cells that do not circulate to SLO on a regular basis. This is reflected by a decrease of naïve and central memory cells and a relative increase of effector memory cells in peripheral blood of fingolimod treated patients. So far, the effect of a concomitant treatment of natalizumab and fingolimod on the immune system has not been studied.