l-Arginine modulates CD3ζ 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 CD3ζ. Following internalization, CD3ζ is degraded and replaced by newly synthesized CD3ζ 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 CD3ζ 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 CD3ζ. In contrast, T cells stimulated and cultured in absence of l-arginine, present a sustained down-regulation of CD3ζ preventing the normal expression of the TCR, exhibit a decreased proliferation, and a significantly diminished production of IFNγ, IL5, and IL10, but not IL2. The replenishment of l-arginine recovers the expression of CD3ζ. The decreased expression of CD3ζ is not caused by a decreased CD3ζ mRNA, an increased CD3ζ degradation or T cell apoptosis.