L-arginine modulates CD3ξ expression and T cell function in activated human T lymphocytes

Engagement of the T cell receptor (TCR) by antigen or anti-CD3 antibody results in a cycle of internalization and re-expression of the CD3 zeta. Following internalization, CD3 zeta is degraded and replaced by newly synthesized CD3 zeta 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 CD3 zeta 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 CD3 zeta. In contrast, T cells stimulated and cultured in absence of L-arginine, present a sustained down-regulation of CD3 zeta preventing the normal expression of the TCR, exhibit a decreased proliferation, and a significantly diminished production of IFN gamma, IL5, and IL10, but not IL2. The replenishment of L-arginine recovers the expression of CD3. The decreased expression of CD3 zeta is not caused by a decreased CD3 zeta mRNA, an increased CD3 zeta degradation or T cell apoptosis. (c) 2005 Elsevier Inc. All rights reserved.