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.
| Original language | English |
|---|---|
| Pages (from-to) | 21-8 |
| Number of pages | 8 |
| Journal | Journal of Neuroimmunology |
| Volume | 96 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Apr 1999 |
Keywords
- 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
- Interleukin-2/biosynthesis
- Lymphocyte Activation/drug effects
- 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
- Vigabatrin
- gamma-Aminobutyric Acid/analogs & derivatives