During neuroinflammation T-cells invade the CNS, and may lead to the development and progression of several pathologies, of which multiple sclerosis is the most common. In these pathologies neuroinflammation is often associated with cognitive dysfunction. Using mouse hippocampal slices, we show here that CD4+CD25– T-cells inhibit long-term potentiation (LTP) induced by high-frequency stimulation. The T-cell-mediated inhibition of LTP can be prevented by blockade of γ-aminobutyric acid (GABA)A receptors. These findings provide additional insight into the multiple functions of T-cells in CNS pathologies.