Increased GABA(A) 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 (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.
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Suresh Kumar
SK
Mendu
Lina
L
Akesson
Zhe
Z
Jin
Anna
A
Edlund
Corrado
C
Cilio
Ake
A
Lernmark
Bryndis
B
Birnir
D000818:Animals; D020296:Animals, Congenic; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011913:Rats, Inbred BB; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid