Clin Immunol Immunopathol. 1997 Apr;83(1):77-85.

Posttranscriptional regulation of T-cell IL-2 production by human pooled immunoglobin.

Modiano JF, Amran D, Lack G, Bradley K, Ball C, Domenico J, Gelfand EW.

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Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.

Abstract

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.

PMID:: 9073539; [PubMed - indexed for MEDLINE]

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