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

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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 - Jan 1 1997

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Interleukin-2
T-Lymphocytes
Firefly Luciferases
Monensin
Jurkat Cells
Immune System Diseases
Globulins
Mitogens
Blood Cells
Cytokines
Messenger RNA
Genes
Proteins

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Posttranscriptional regulation of T-cell IL-2 production by human pooled immunoglobin. / Modiano, Jaime F.; Amran, David; Lack, Gideon; Bradley, Katherine; Ball, Carrie; Domenico, Joanne; Gelfand, Erwin W.

In: Clinical Immunology and Immunopathology, Vol. 83, No. 1, 01.01.1997, p. 77-85.

Research output: Contribution to journalArticle

Modiano, Jaime F. ; Amran, David ; Lack, Gideon ; Bradley, Katherine ; Ball, Carrie ; Domenico, Joanne ; Gelfand, Erwin W. / Posttranscriptional regulation of T-cell IL-2 production by human pooled immunoglobin. In: Clinical Immunology and Immunopathology. 1997 ; Vol. 83, No. 1. pp. 77-85.
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