L-arginine metabolism in myeloid cells controls T-lymphocyte functions

Trends Immunol. 2003 Jun;24(6):302-6. doi: 10.1016/s1471-4906(03)00132-7.


Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways.

Publication types

  • Review

MeSH terms

  • Animals
  • Arginase / metabolism
  • Arginine / metabolism*
  • Humans
  • Immunity, Cellular / physiology*
  • Interleukin-2 / metabolism
  • Myeloid Cells / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Suppressor Factors, Immunologic / metabolism*
  • T-Lymphocytes / metabolism*


  • Interleukin-2
  • Suppressor Factors, Immunologic
  • Arginine
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Arginase