Role reversal: infiltrating T cells protect the brain.

Inflammatory conditions intensify and then resolve, often sparing and recovering some of the injured tissue. While the ebb and flow of inflammation can be followed in many tissues, there is not a great deal of information on how inflammation regresses in the brain. In this issue of the JCI, Walsh, Hendrix, and colleagues illuminate a cellular mechanism whereby T cells that infiltrate the brain after nerve crush or contusion actually protect neurons from injury. These infiltrating T cells produce IL-4 and do so independently of a classic adaptive T cell immune response. The T cells respond to mediators produced by damaged neurons, without the classic three-way interaction among antigen, the major histocompatibility complex, and the T cell receptor. After brain injury, these protective T cells produce IL-4, which attenuates damage via IL-4 receptors on neurons.