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

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 (DRlyp/lyp) or resistant (DR+/+) congenic biobreeding (BB) rats for expression of GABAA channels. Our results show that BB rat CD4+ and CD8+ T cells express α1, α2, α3, α4, α6, β3, γ1, δ, ρ1 and ρ2 GABAA channel subunits. In CD8+ T cells from DRlyp/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 DRlyp/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.