On page 1805, Kawakami et al. show that antigen-specific CD4+ T cells that attack the brain become stationary within brain tissue, whereas nonspecific T cells cruise through without stopping. These intravital images—the first to capture T cells launching an autoimmune attack on the brain—suggest that antigen-specific T cells behave similarly in dense brain tissue as they do in lymph nodes.

A subset of MBP-specific T cells (green) become stationary in the brain during EAE, presumably after engaging their antigen on antigen-presenting cells (red).

Activated CD4+ T cells specific for the endogenous brain protein myelin basic protein (MBP) trigger fatal encephalomyelitis in a rat model of multiple sclerosis. These cells migrate into the central nervous system (CNS) where they become reactivated.

Previous studies by this group showed that both antigen-specific and nonspecific T cells gain access to the CNS, but only specific cells become reactivated once there. Kawakami et al. now show that a subset of MBP-specific T cells—likely those that have encountered antigen—stopped moving inside the brain, appearing tethered to a fixed point. T cells specific for a control antigen kept moving, suggesting that the presence of antigen was required for T cells to stop moving and to trigger disease.

The authors were surprised to find that T cells move as rapidly through the dense brain tissue as in the more aqueous environment of the lymph nodes. How they do this is not known but the authors suggest that the T cells may produce proteases that help clear a path through the compact tissue.