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.
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Fehervari, Z. Healing the CNS. Nat Immunol 16, 228 (2015). https://doi.org/10.1038/ni.3111
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DOI: https://doi.org/10.1038/ni.3111