HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tian, J. Articles by Kaufman, D. L. Search for Related Content PubMed PubMed Citation Articles by Tian, J. Articles by Kaufman, D. L.

-Aminobutyric Acid Inhibits T Cell Autoimmunity and the Development of Inflammatory Responses in a Mouse Type 1 Diabetes Model¹

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095

-Aminobutyric acid (GABA) is both a major inhibitory neurotransmitter in the CNS and a product of cells of the peripheral islets. Our previous studies, and those of others, have shown that T cells express functional GABA_A receptors. However, their subunit composition and physiological relevance are unknown. In this study, we show that a subset of GABA_A receptor subunits are expressed by CD4⁺ T cells, including the subunit that confers high affinity for GABA and sensitivity to alcohol. GABA at relatively low concentrations down-regulated effector T cell responses to cell Ags ex vivo, and administration of GABA retarded the adoptive transfer of type 1 diabetes (T1D) in NOD/scid mice. Furthermore, treatment with low dose of GABA (600 µg daily) dramatically inhibited the development of proinflammatory T cell responses and disease progression in T1D-prone NOD mice that already had established autoimmunity. Finally, GABA inhibited TCR-mediated T cell cycle progression in vitro, which may underlie GABA’s therapeutic effects. The immunoinhibitory effects of GABA on T cells may contribute to the long prodomal period preceding the development of T1D, the immunological privilege of the CNS, and the regulatory effects of alcohol on immune responses. Potentially, pharmacological modulation of GABA_A receptors on T cells may provide a new class of therapies for human T1D as well as other inflammatory diseases.

This article has been cited by other articles:

				J. Tian, H. Dang, H. von Boehmer, E. Jaeckel, and D. L. Kaufman Transgenically Induced GAD Tolerance Curtails the Development of Early {beta}-Cell Autoreactivities but Causes the Subsequent Development of Supernormal Autoreactivities to Other {beta}-Cell Antigens Diabetes, December 1, 2009; 58(12): 2843 - 2850. [Abstract] [Full Text] [PDF]

				Y. Wang, D. Feng, G. Liu, Q. Luo, Y. Xu, S. Lin, J. Fei, and L. Xu {gamma}-Aminobutyric Acid Transporter 1 Negatively Regulates T Cell-Mediated Immune Responses and Ameliorates Autoimmune Inflammation in the CNS J. Immunol., December 15, 2008; 181(12): 8226 - 8236. [Abstract] [Full Text] [PDF]

				M. E. Munroe, J. L. Arbiser, and G. A. Bishop Honokiol, a Natural Plant Product, Inhibits Inflammatory Signals and Alleviates Inflammatory Arthritis J. Immunol., July 15, 2007; 179(2): 753 - 763. [Abstract] [Full Text] [PDF]

				C. Wang, R. Mao, M. Van De Casteele, D. Pipeleers, and Z. Ling Glucagon-like peptide-1 stimulates GABA formation by pancreatic beta-cells at the level of glutamate decarboxylase Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1201 - E1206. [Abstract] [Full Text] [PDF]

				C. Wang, K. Kerckhofs, M. Van de Casteele, I. Smolders, D. Pipeleers, and Z. Ling Glucose inhibits GABA release by pancreatic beta-cells through an increase in GABA shunt activity Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E494 - E499. [Abstract] [Full Text] [PDF]