L-Arginine modulates CD3zeta 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.
Zea
Arnold H
AH
Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA. azea@lsuhsc.edu
Rodriguez
Paulo C
PC
Culotta
Kirk S
KS
Hernandez
Claudia P
CP
DeSalvo
Joanna
J
Ochoa
Juan B
JB
Park
Hae-Joon
HJ
Zabaleta
Jovanny
J
Ochoa
Augusto C
AC
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001120:Arginine / Q000494:pharmacology*; D017252:CD3 Complex / Q000187:drug effects* / Q000235:genetics* / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D016207:Cytokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D001120:Arginine; D002118:Calcium