GABA(A) receptors mediate inhibition of T cell responses.
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.
Tian
J
J
Department of Molecular and Medical Pharmacology, University of California, Los Angeles 90095-1735, USA.
Chau
C
C
Hales
T G
TG
Kaufman
D L
DL
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D001640:Bicuculline / Q000494:pharmacology; D017252:CD3 Complex / Q000032:analysis; D002455:Cell Division / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006968:Hypersensitivity, Delayed; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000276:immunology*; D018080:Receptors, GABA-B / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000276:immunology*; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000578:Amidines; D001640:Bicuculline; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D007376:Interleukin-2; D009118:Muscimol; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid