GABA A receptors mediate inhibition of T cell responses

• Published in: Journal of neuroimmunology 1999-04, Vol.96 (1), p.21-28
• Main Authors: Tian, Jide, Chau, Cindy, Hales, Tim G, Kaufman, Daniel L
• Format: Article
• Language: English
• Subjects: Amidines - pharmacology; Animals; Autocrine Communication - immunology; Bicuculline - pharmacology; CD3 Complex - analysis; Cell Division - immunology; Cytokine; DTH; Enzyme Inhibitors - pharmacology; Female; GABA; GABA Agonists - pharmacology; GABA Antagonists - pharmacology; GABA Modulators - pharmacology; GABA receptor; gamma-Aminobutyric Acid - analogs & derivatives; gamma-Aminobutyric Acid - pharmacology; Hypersensitivity, Delayed; Immunosuppression; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes; Male; Mice; Mice, Inbred NOD; Muscimol - pharmacology; Pentobarbital - pharmacology; Picrotoxin - pharmacology; Receptors, GABA-A - immunology; Receptors, GABA-B - immunology; Signal Transduction - immunology; T cell proliferation; T-Lymphocytes - chemistry; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Vigabatrin
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(98)00264-1

We describe the presence of functional GABA A receptors on T cells. GABA inhibited anti-CD3 and antigen-specific T cell proliferation in vitro in a dose-dependent manner that was 1) mimicked by the GABA A receptor agonist muscimol (but not the GABA B receptor agonist baclofen), 2) blocked by GABA A receptor antagonists and a GABA A receptor Cl − channel blocker (picrotoxin) and 3) enhanced by pentobarbital. These data suggest that GABA A receptors mediate this immune inhibition and that these receptors can be modulated in a similar fashion to their neuronal counterparts. Finally, GABA inhibited DTH responses in vivo. Thus, pharmacological modulation of GABA A receptors may provide new approaches to modulate T cell responses in inflammation and autoimmune disease.