Brain-Resident CD8 ⁺ T Cells Regulate Neuronal Activity and Behavior via Interferon-Gamma

Maintaining brain homeostasis is crucial for proper function of the central nervous system and has traditionally been attributed to neuronal and glial interactions. However, recent research highlights the essential role of brain-resident immune cells in this process. Our study characterizes brain-specific CD8 ⁺ T cells and elucidates their significant contribution to brain homeostasis and behavior. We identified a distinct population of CD8 ⁺ T cells that infiltrates the brain during early development, undergoes clonal expansion, and acquires effector memory-like characteristics through interactions with microglia. Notably, the absence of these cells results in hyperactivation of neuronal activity and abnormal behaviors, due to loss of regulation of interferon-gamma (IFN-γ) secreted by CD8 ⁺ T cells. Our findings demonstrate that IFN-γ secreting brain-specific CD8 ⁺ T cells are crucial for maintaining the physiological level of neuronal excitability and normal behavioral patterns. This study provides novel insights into neuroimmune interactions, emphasizing the critical role of CD8 ⁺ T cells in sustaining brain function and behavior.