Published in:
01-05-2010
sHLA-I Contamination, A Novel Mechanism to Explain Ex Vivo/In Vitro Modulation of IL-10 Synthesis and Release in CD8+ T Lymphocytes and in Neutrophils Following Intravenous Immunoglobulin Infusion
Authors:
Massimo Ghio, Paola Contini, Maurizio Setti, Gianluca Ubezio, Clemente Mazzei, Gino Tripodi
Published in:
Journal of Clinical Immunology
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Issue 3/2010
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Abstract
Background
Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders; among others, they could decrease pro-inflammatory cytokine levels and also induce anti-inflammatory cytokines.
Materials and Methods
Ex vivo analysis of cells from ten IVIG recipients showed significant increase of IL-10 mRNA and intra-cellular IL-10 molecules in both leukotypes.
Results
In vitro comparable results were obtained incubating CD8+ T lymphocytes and neutrophils from healthy donors with IVIG. sHLA-I and/or sFasL immunodepletion abolished IL-10 modulation. Co-culture with contaminant-free IgM or MabThera did not exert any mRNA modulation. Finally, IgM or MabThera plus purified sHLA-I molecules enhanced IL-10-mRNA in both leukotypes to levels comparable to those obtained with IVIG incubation.
Conclusion
As IVIG infusion involves administration of soluble contaminants, these data consent to speculate that IVIG might modulate IL-10 via the immunomodulatory activities of sHLA-I contaminant molecules inducing transcriptional and post-transcriptional modulation of IL-10 in CD8+ T lymphocytes and neutrophils.