Intravenous immunoglobulin G-mediated inhibition of T-cell proliferation reflects an endogenous mechanism by which IgG modulates T-cell activation

Commercial intravenous immunoglobulin G (IVIG) at high doses has therapeutic benefit in autoimmune and inflammatory diseases. It has been shown to inhibit T-cell function but the mechanisms are unclear. Inhibition could result from IVIG processing, donor pooling or intrinsic downregulatory activity...

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Publié dans:Clinical immunology (Orlando, Fla.). - 1999. - 132(2009), 2 vom: 01. Aug., Seite 222-33
Auteur principal: MacMillan, Heather F (Auteur)
Autres auteurs: Lee, Tim, Issekutz, Andrew C
Format: Article en ligne
Langue:English
Publié: 2009
Accès à la collection:Clinical immunology (Orlando, Fla.)
Sujets:Journal Article Research Support, Non-U.S. Gov't Antibodies, Monoclonal CD28 Antigens CD3 Complex Immunoglobulin Fab Fragments Immunoglobulin G Immunoglobulins, Intravenous Receptors, Antigen, T-Cell
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245 1 0 |a Intravenous immunoglobulin G-mediated inhibition of T-cell proliferation reflects an endogenous mechanism by which IgG modulates T-cell activation 
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520 |a Commercial intravenous immunoglobulin G (IVIG) at high doses has therapeutic benefit in autoimmune and inflammatory diseases. It has been shown to inhibit T-cell function but the mechanisms are unclear. Inhibition could result from IVIG processing, donor pooling or intrinsic downregulatory activity of IgG. To address these points, we compared the effects on T-cell activation of IVIG, Fab(2) fragment and IgG isolated from single-donor plasma. We also investigated the role of accessory cells in the IVIG effects using highly purified T cells stimulated through CD3 and CD28 engagement. T-cell proliferation was evaluated by Oregon Green 488 dye dilution and (3)H-thymidine incorporation. IVIG, Fab(2) fragment of IVIG and autologous, single-donor IgG significantly inhibited T-cell proliferation (35-50%), even in the absence of accessory cells. Depletion of IgG from plasma used for culture significantly increased (by 50%) the T-cell proliferation. The addition of physiological concentrations of single-donor, autologous IgG or IVIG to IgG-depleted plasma reduced T-cell proliferation to levels observed in normal plasma. Therefore, donor pooling in IVIG and accessory cells are not required for inhibition of T-cell proliferation by IVIG and the Fab(2) region is sufficient to mediate this inhibition. Suppression of T-cell activation by IVIG likely reflects a physiologic, endogenous mechanism of IgG-mediated regulation of T-cell activation 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Antibodies, Monoclonal  |2 NLM 
650 7 |a CD28 Antigens  |2 NLM 
650 7 |a CD3 Complex  |2 NLM 
650 7 |a Immunoglobulin Fab Fragments  |2 NLM 
650 7 |a Immunoglobulin G  |2 NLM 
650 7 |a Immunoglobulins, Intravenous  |2 NLM 
650 7 |a Receptors, Antigen, T-Cell  |2 NLM 
700 1 |a Lee, Tim  |e verfasserin  |4 aut 
700 1 |a Issekutz, Andrew C  |e verfasserin  |4 aut 
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856 4 0 |u http://dx.doi.org/10.1016/j.clim.2009.04.002  |3 Volltext 
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