T cells serve both neurodegenerative roles and neuroprotective roles in the central nervous system (CNS). In the Journal of Clinical Investigation, Kipnis and colleagues characterize the mechanism of T cell–mediated neuroprotection in two mouse models of CNS injury. CD4+ T cells are found at sites of CNS injury, and their presence correlates with neuronal protection and functional recovery. The beneficial effect of these CD4+ T cells is dependent on their production of IL-4 but independent of antigen presentation or recognition of any obvious CNS antigen. Instead, the infiltrating T cells are activated to produce IL-4 in a bystander manner by as-yet-unidentified alarmins released from the injured CNS that act via adaptor MyD88–dependent receptors on the T cells. The IL-4 released by the T cells acts directly on neurons and acts together with other neurotrophic factors to support neuronal growth and repair.

J. Clin. Invest. (20 January 2015) doi:10.1172/JCI76210