Type 1 lymphocytes and interferon-γ accumulate in the thalamus and restrict seizure susceptibility after traumatic brain injury

Chronic neural circuit hyperexcitability frequently emerges after brain injury, but endogenous mechanisms constraining runaway activity remain poorly understood. Here, we reveal that the adaptive immune system acts as a homeostatic brake on network excitability following traumatic brain injury (TBI). In mice, cortical trauma triggered a delayed infiltration of interferon-γ (IFNγ)–producing type 1 lymphocytes into the sensory thalamus. Rather than driving pathology, IFNγ signaling directly in neurons restricted thalamocortical network hyperexcitability. This protective axis was tonically regulated; depleting CD4⁺ T cells de-repressed local non-CD4⁺ type 1 lymphocytes, elevating IFNγ signaling and protecting from seizures. A single dose of exogenous IFNγ abolished hypersynchronous circuit bursting and rescued injury-induced seizure incidence, severity, and mortality, establishing a therapeutic framework for safeguarding circuit stability after brain injury.