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 u nresponsiveness in T cells to further stimulation, a phenomenon known as anergy. In freshly isolated T cells, calcium ionophore induces expr ession of interleukin (IL)-2 messenger (nRNA), but this mRNA is not tr anslated 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 cont rolled at the translational level, by differential ribosome loading. F urthermore, our data suggest that translational control of IL-2 nRNA m ay be a molecular mechanism by which anergy is attained.