l-Arginine modulates CD3ζ expression and T cell function in activated human T lymphocytes
Copyright policy )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 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.
- Tulane University United States
- Louisiana State University Health Sciences Center New Orleans United States
- The University of Texas MD Anderson Cancer Center United States
- University of Pittsburgh United States
CD3 Complex, T-Lymphocytes, Receptors, Antigen, T-Cell, Apoptosis, Arginine, Lymphocyte Activation, Gene Expression Regulation, Cytokines, Humans, Tyrosine, Calcium, RNA, Messenger, Phosphorylation, Cells, Cultured, Cell Proliferation
CD3 Complex, T-Lymphocytes, Receptors, Antigen, T-Cell, Apoptosis, Arginine, Lymphocyte Activation, Gene Expression Regulation, Cytokines, Humans, Tyrosine, Calcium, RNA, Messenger, Phosphorylation, Cells, Cultured, Cell Proliferation
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