Translational control of interleukin 2 messenger RNA as a molecular mechanism of T cell anergy.
T cell stimulation by triggering through the T cell receptor (TCR) in the absence of costimulatory signals or by calcium ionophore induces unresponsiveness in T cells to further stimulation, a phenomenon known as anergy. In freshly isolated T cells, calcium ionophore induces expression of interleukin (IL)-2 messenger (mRNA), but this mRNA is not translated and not loaded with ribosomes. In addition, while plate-bound anti-CD3 stimulation of resting T cells leads to IL-2 mRNA expression and IL-2 secretion, in cells pretreated with calcium ionophore before anti-CD3 stimulation, the IL-2 mRNA remains polysome unloaded and no IL-2 is produced. These observations show that IL-2 expression is controlled at the translational level, by differential ribosome loading. Furthermore, our data suggest that translational control of IL-2 mRNA may be a molecular mechanism by which anergy is attained.
Garcia-Sanz
J A
JA
Basel Institute for Immunology, Switzerland.
Lenig
D
D
D001483:Base Sequence; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D017635:Clonal Anergy; D017931:DNA Primers / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007476:Ionophores / Q000494:pharmacology; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017931:DNA Primers; D007376:Interleukin-2; D007476:Ionophores; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium