Retinotectal Mapping without EphA Receptors

Autoimmune disease is accompanied by T-cell invasion of the CNS, a realm from which they are normally banned. But while we generally think of oligodendrocytes as the primary victims in demyelinating autoimmune disorders such as multiple sclerosis (MS), Nitsch et al. show this week that neurons themselves are under attack from T cells as well. The authors exposed mouse brain slices with intact cellular architecture to activated T cells. T cells were stimulated with oligodendrocytederived proteolipid protein (PLP) or ovalbumin (not expressed in mice). The T cells encountered, bound, and killed neurons, whereas unstimulated T cells did not invade the slice. Using two-photon microscopy and ion-sensitive dyes, the authors tracked the real-time movements of the stimulated T cells. T cells, traveling quickly (2.5 m/sec at 34°C), assailed neurons with a veritable neuronal kryptonite: calcium oscillations. They identified two seemingly cooperative pathways for the excitotoxic calcium: perforin release from T cells and neuronal glutamate receptor activation. Click the movie and watch them go!