Regulation of T cell receptor CD3zeta chain expression by L-arginine.
L-Arg plays a central role in the normal function of several organ systems including the immune system. L-Arg can be depleted by arginase I produced by macrophages and hepatocytes in several disease states such as trauma and sepsis and following liver transplantation. The decrease in L-Arg levels induces a profound decrease in T cell function through mechanisms that have remained unclear. The data presented here demonstrate that Jurkat T cells cultured in medium without L-Arg (L-Arg-free RPMI) have a rapid decrease in the expression of the T cell antigen receptor zeta chain (CD3zeta), the principal signal transduction element in this receptor, and a decrease in T cell proliferation. This phenomenon is completely reversed by the replenishment of L-Arg but not other amino acids. These changes are not caused by cell apoptosis; instead, the diminished expression of CD3zeta protein is paralleled by a decrease in CD3zeta mRNA. This change in CD3zeta mRNA expression is not caused by a decrease in the transcription rate but rather by a significantly shorter CD3zeta mRNA half-life. This mechanism is sensitive to cycloheximide. Therefore, the regulation of L-Arg concentration in the microenvironment could represent an important mechanism to modulate the expression of CD3zeta and the T cell receptor and consequently of T cell function.
Rodriguez
Paulo C
PC
Tumor Immunology Program, Stanley S. Scott Cancer Center and Department of Pediatrics, Louisiana State University, Health Sciences Center, New Orleans, Louisiana 70112, USA.
Zea
Arnold H
AH
Culotta
Kirk S
KS
Zabaleta
Jovanny
J
Ochoa
Juan B
JB
Ochoa
Augusto C
AC
D000818:Animals; D017209:Apoptosis; D001120:Arginine / Q000737:chemistry* / Q000378:metabolism; D015152:Blotting, Northern; D017252:CD3 Complex / Q000737:chemistry*; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D005434:Flow Cytometry; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D017252:CD3 Complex; D018076:DNA, Complementary; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D003609:Dactinomycin; D001120:Arginine; D003513:Cycloheximide