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-related immunodeficiencies. We have investigated the molecular mechanisms involved in the decrease of IL-2 production in CD4+ T cells from aging mice. Our results demonstrate that the stability of IL-2 mRNA increases in T cells from young mice, whereas it declines in T cells from old mice with the time of stimulation, suggesting the existence of different mechanisms of post-transcriptional regulation in young and old mice. We found that the IL-2 mRNA level in T cells from young but not from old mice increased up to 6- to 10-fold by addition of cycloheximide (CHX) while the stability of IL-2 mRNA is not affected. We then looked 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, yet, 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.
Pucci
S
S
Laboratory of Immunology, AMB-PRO-TOSS, ENEA CR Casaccia, St Maria di Galeria (Rome), Italy.
Doria
G
G
Barile
S
S
Pioli
C
C
Frasca
D
D
D000367:Age Factors; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016335:Zinc Fingers / Q000502:physiology*
D007376:Interleukin-2; D012333:RNA, Messenger; D003513:Cycloheximide