GABA, a natural immunomodulator of T lymphocytes

γ-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low (nM–1 µM), physiological concentrations of GABA present around neurons in the brain. The cells expressed the α1, α4, β2, β3, γ1 and δ GABAA channel subunits and formed functional, extrasynaptic-like GABA channels that were activated by 1 µM GABA. 100 nM and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory.