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

Jaime F. Modiano, David Amran, Gideon Lack, Katherine Bradley, Carrie Ball, Joanne Domenico, Erwin W. Gelfand

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

We evaluated the mechanism by which human pooled γ-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 posttranscriptionally, 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.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalClinical Immunology and Immunopathology
Volume83
Issue number1
DOIs
StatePublished - Apr 1997

Bibliographical note

Funding Information:
This work was supported in part by Grant HL-36577 (E.W.G.) and by a grant from Bayer Pharmaceuticals. J.F.M. was supported by Clinical Investigator Development Award HL-03130 from the National Institutes of Health. We thank Dr. T. Baldwin and V. Crane for assistance with luminescence assays, Drs. N. Terada, J. Lucas, and C. Chitko-McKown for helpful discussions, Diana Nabighian for editorial assistance, and the staff of the Blood Banks from the Children's Hospital, Denver, and the Scott and White Blood Center in Temple, TX, for their assistance in providing plateletpheresis residues.

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