INHIBITION OF IL-2 PRODUCTION BY NIL-2-A IN MURINE T-CELLS

The loss of IL-2 production is the main defect accounting for age-rela ted immunodeficiencies. We have investigated the molecular mechanisms involved in the decrease of IL-2 production in CD4(+) T cells from agi ng mice. Our results demonstrate that the stability of IL-2 mRNA incre ases in T cells from young mice, whereas it declines in T cells from o ld mice with the time of stimulation, suggesting the existence of diff erent mechanisms of post-transcriptional regulation in young and old m ice. We found that the IL-2 mRNA level in T cells from young but not f rom old mice increased up to 6- to 10-fold by addition of cycloheximid e (CHX) while the stability of IL-2 mRNA is not affected. We then look ed for IL-2 inducible inhibitory factors in T cells from young and old mice and demonstrated the presence of Nil-2-a, a zinc finger protein which negatively controls IL-2 gene transcription in human cells. This protein could be detected in T cells from both young and old mice, ye t, in the presence of CHX, its binding activity was reduced by 75% in T cells from young but not from old mice. These findings show that Nil -2-a accounts for the negative control of IL-2 production in the mouse and explain the reduced IL-2 production in aging.