Increased GABA(A) channel subunits expression in CD8(+) but not in CD4(+) T cells in BB rats developing diabetes compared to their congenic littermates

Mol Immunol. 2011 Jan;48(4):399-407. doi: 10.1016/j.molimm.2010.08.005. Epub 2010 Nov 26.


GABA (γ-aminobutyric acid), the main inhibitory neurotransmitter in the central nervous system is also present in the pancreatic islet β cells where it may function as a paracrine molecule and perhaps as an immunomodulator of lymphocytes infiltrating the pancreatic islet. We examined CD4(+) and CD8(+) T cells from diabetes prone (DR(lyp/lyp)) or resistant (DR(+/+)) congenic biobreeding (BB) rats for expression of GABA(A) channels. Our results show that BB rat CD4(+) and CD8(+) T cells express α1, α2, α3, α4, α6, β3, γ1, δ, ρ1 and ρ2 GABA(A) channel subunits. In CD8(+) T cells from DR(lyp/lyp) animals the subunits were significantly upregulated relative to expression levels in the CD8(+) T cells from DR(+/+) rats as well as from CD4(+) T cells from both DR(lyp/lyp) and DR(+/+) rats. Functional channels were formed in the T cells and physiological concentrations of GABA (100 nM) decreased T cell proliferation. Our results are consistent with the hypothesis that GABA in the islets of Langerhans may diminish inflammation by inhibition of activated T lymphocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Congenic
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Proliferation / drug effects
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology*
  • Gene Expression Regulation / drug effects
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Rats
  • Rats, Inbred BB
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • gamma-Aminobutyric Acid / pharmacology


  • Protein Subunits
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid