L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes

Cell Immunol. 2004 Nov-Dec;232(1-2):21-31. doi: 10.1016/j.cellimm.2005.01.004. Epub 2005 Feb 23.


Engagement of the T cell receptor (TCR) by antigen or anti-CD3 antibody results in a cycle of internalization and re-expression of the CD3zeta. Following internalization, CD3zeta is degraded and replaced by newly synthesized CD3zeta on the cell surface. Here, we provide evidence that availability of the amino acid L-arginine modulates the cycle of internalization and re-expression of CD3zeta and cause T cell dysfunction. T cells stimulated and cultured in presence of L-arginine, undergo the normal cycle of internalization and re-expression of CD3zeta. In contrast, T cells stimulated and cultured in absence of L-arginine, present a sustained down-regulation of CD3zeta preventing the normal expression of the TCR, exhibit a decreased proliferation, and a significantly diminished production of IFNgamma, IL5, and IL10, but not IL2. The replenishment of L-arginine recovers the expression of CD3zeta. The decreased expression of CD3zeta is not caused by a decreased CD3zeta mRNA, an increased CD3zeta degradation or T cell apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Arginine / pharmacology*
  • CD3 Complex / drug effects*
  • CD3 Complex / genetics*
  • CD3 Complex / immunology
  • Calcium / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • Phosphorylation
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / drug effects
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tyrosine / metabolism


  • CD3 Complex
  • CD3 antigen, zeta chain
  • Cytokines
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Tyrosine
  • Arginine
  • Calcium