GABA(A) receptors mediate inhibition of T cell responses

J Neuroimmunol. 1999 Apr 1;96(1):21-8. doi: 10.1016/s0165-5728(98)00264-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amidines / pharmacology
  • Animals
  • Autocrine Communication / immunology
  • Bicuculline / pharmacology
  • CD3 Complex / analysis
  • Cell Division / immunology
  • Enzyme Inhibitors / pharmacology
  • Female
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • GABA Modulators / pharmacology
  • Hypersensitivity, Delayed*
  • Immunosuppression Therapy
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Muscimol / pharmacology
  • Pentobarbital / pharmacology
  • Picrotoxin / pharmacology
  • Receptors, GABA-A / immunology*
  • Receptors, GABA-B / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes / chemistry*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Vigabatrin
  • gamma-Aminobutyric Acid / analogs & derivatives
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amidines
  • CD3 Complex
  • Enzyme Inhibitors
  • GABA Agonists
  • GABA Antagonists
  • GABA Modulators
  • Interleukin-2
  • Receptors, GABA-A
  • Receptors, GABA-B
  • Picrotoxin
  • Muscimol
  • gamma-Aminobutyric Acid
  • Vigabatrin
  • Pentobarbital
  • Bicuculline