Posttranscriptional regulation of T-cell IL-2 production by human pooled immunoglobin.
We evaluated the mechanism by which human pooled gamma-globulin for intravenous use (hIVIG) inhibits interleukin-2 (IL-2) production by human T cells. hIVIG reduced by 70-95% the amount of IL-2 in culture supernatants from mitogen-stimulated peripheral blood T cells or Jurkat cells. This reduction was not apparent at the transcriptional level: hIVIG had no effect on the levels of IL-2 mRNA or on the accumulation of firefly luciferase when its gene was linked to the IL-2 promoters. In contrast, hIVIG inhibited IL-2 protein synthesis, and the intracellular IL-2 was not restored by monensin. Our results indicate that the inhibition of IL-2 production by hIVIG occurred post-transcriptionally, and also suggest that secretion was unaffected, and that this effect of hIVIG was specific for IL-2 (and possibly other related cytokines). The data identify a previously uncharacterized regulatory mechanism of IL-2 production and predict that this immunomodulatory effect of hIVIG may be significant for its therapeutic actions in immune-mediated diseases.
Modiano
J F
JF
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Amran
D
D
Lack
G
G
Bradley
K
K
Ball
C
C
Domenico
J
J
Gelfand
E W
EW
D000328:Adult; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000235:genetics* / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D016756:Immunoglobulins, Intravenous; D007376:Interleukin-2; D012333:RNA, Messenger