Peripheral CD4+ T cells have a central role in multiple sclerosis, but how these cells cross the blood–brain barrier is not understood. Here, the authors examined this issue in a mouse model of the disease. In mice with experimental autoimmune encephalomyelitis, CD4+ T cells accumulated in the lumbar spinal cord. The accumulation was due to the activation of sensory neurons by soleus muscle contractions, which changed blood flow speed in the lumbar region. This induced interleukin-6 amplifier activation in endothelial cells and, consequently, increased chemokine (C-C motif) ligand 20 (CCL20) expression, which was required for CD4+ T cell accumulation. Thus, regional neural activity creates gateways in local blood vessels through which T cells enter the CNS.