Glycine inhibits growth of T lymphocytes by an IL-2-independent mechanism

J Immunol. 2000 Jan 1;164(1):176-82. doi: 10.4049/jimmunol.164.1.176.

Abstract

Previously, it was shown that glycine prevented increases in intracellular calcium ([Ca2+]i) in Kupffer cells. Since Kupffer cells and T lymphocytes are derived from the same pluripotent stem cell, it was hypothesized that glycine would prevent increases in [Ca2+]i in lymphocytes and inhibit cell proliferation. Lymphocyte proliferation was measured in one-way MLC with spleen cells from DA and Lewis rats and in enriched T lymphocyte preparations stimulated by immobilized anti-CD3 Ab. Glycine caused a dose-dependent decrease in cell proliferation to about 40% of control. Con A caused a dose-dependent increase in [Ca2+]i in Jurkat cells which was blunted maximally with 0.6 mM glycine. The effect of glycine was dependent on extracellular chloride and reversed by strychnine, an antagonist of the glycine-gated chloride channel. Similar results were obtained with rat T lymphocytes stimulated by anti-CD3 Ab. Surprisingly, glycine had no effect on IL-2 production in the mixed lymphocyte culture; therefore, the effect of glycine on IL-2-dependent proliferation was tested. Glycine and rapamycin caused dose-dependent decreases in IL-2-stimulated growth of Ctll-2 cells to about 60% and 40%, respectively, of control. Moreover, glycine also inhibited the IL-2-stimulated growth of rat splenic lymphocytes. It is concluded that glycine blunts proliferation in an IL-2-independent manner. This is consistent with the hypothesis that glycine activates a glycine-gated chloride channel and hyperpolarizes the cell membrane-blunting increases in [Ca2+]i that are required for transcription of factors necessary for cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD3 Complex / immunology
  • Calcium / metabolism
  • Cell Division / drug effects
  • Cell Division / immunology
  • Chloride Channel Agonists
  • Concanavalin A / pharmacology
  • Cyclosporine / pharmacology
  • Female
  • Glycine / agonists
  • Glycine / physiology*
  • Growth Inhibitors / agonists
  • Growth Inhibitors / pharmacology
  • Growth Inhibitors / physiology*
  • Humans
  • Immune Sera / pharmacology
  • Interleukin-2 / physiology*
  • Intracellular Fluid / metabolism
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Lymphocyte Culture Test, Mixed
  • Rats
  • Rats, Inbred Lew
  • Strychnine / agonists
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • CD3 Complex
  • Chloride Channel Agonists
  • Growth Inhibitors
  • Immune Sera
  • Interleukin-2
  • Concanavalin A
  • Cyclosporine
  • Strychnine
  • Calcium
  • Glycine