The neurotransmitter gamma-amino butyric acid (GABA) modulates T cell proliferation

DIONISIO, L.; DE ROSA, M.J.; BOUZAT, C.; ESANDI, M.C.

Bahía Blanca, Buenos Aires

Workshop; Workshop Neuronal Communication: from structure to physiology; 2008

Increasing evidence suggests the occurrence of relationships between immune and neuroendocrine systems. Many cells of the immune system express receptors for neuroactive molecules. GABA is a ubiquitous inhibitory neurotransmitter in the central nervous system. The goal of this study was to determine if components of the GABAergic system are expressed in lymphocytes and whether their presence had any functional significance. Using RT-PCR we analyzed expression of mRNA of different components of this system in resting and activated lymphocytes (PHA 10 mg/ml). We determined mRNA expression of: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, a vesicular protein that is involved in GABA store; iii) GABA transporters (GAT1 and GAT2); iv) GABA-t, an enzyme that catabolizes GABA; v) alpha subunits (a1, a3 and a6) of GABAA receptor; and vi) the rho 2 subunit of the GABAC receptor. The functionality of the transporters was evaluated by measuring uptake of radioactive GABA. The results demonstrated that the uptake of GABA is significantly higher in activated lymphocytes than in resting ones. Finally, using a proliferation assay, we established that GABA is able to modulate lymphocyte proliferation in a concentration dependent manner.  Our results revealed that lymphocytes have most of the essential components needed to constitute a non neuronal GABAergic system. Pharmacological modulation of this system may provide new approaches for regulation of T cell response. Furthermore, elucidation of its function will contribute to clarify the interactions between the nervous and immune systems.