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Suppression of T-cell functions by human granulocyte arginase

Chronic inflammation is accompanied by impaired T-cell immunity. In the mouse, myeloid cell-associated arginase accounts for the suppression of immune reactivity in various models of tumor growth and chronic infections. Here we show that arginase I is liberated from human granulocytes, and very high...

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Main Authors: Munder, Markus (Author) , Rudolph, Henriette (Author) , Luckner-Minden, Claudia (Author) , Giese, Thomas (Author) , Langhans, Claus-Dieter (Author) , Fuentes, Jose M. (Author) , Kropf, Pascale (Author) , Mueller, Ingrid (Author) , Kolb, Armin (Author) , Modolell, Manuel (Author) , Ho, Anthony Dick (Author)
Format: Article (Journal)
Language:English
Published: September 1, 2006
In: Blood
Year: 2006, Volume: 108, Issue: 5, Pages: 1627-1634
ISSN:1528-0020
DOI:10.1182/blood-2006-11-010389
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2006-11-010389
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Author Notes:Markus Munder, Henriette Schneider, Claudia Luckner, Thomas Giese, Claus-Dieter Langhans, Jose M. Fuentes, Pascale Kropf, Ingrid Mueller, Armin Kolb, Manuel Modolell, and Anthony D. Ho
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Summary:Chronic inflammation is accompanied by impaired T-cell immunity. In the mouse, myeloid cell-associated arginase accounts for the suppression of immune reactivity in various models of tumor growth and chronic infections. Here we show that arginase I is liberated from human granulocytes, and very high activities accumulate extracellularly during purulent inflammatory reactions. Human granulocyte arginase induces a profound suppression of T-cell proliferation and cytokine synthesis. This T-cell phenotype is due to arginase-mediated depletion of arginine in the T-cell environment, which leads to CD3ζ chain down-regulation but does not alter T-cell viability. Our study therefore demonstrates that human granulocytes possess a previously unanticipated immunosuppressive effector function. Human granulocyte arginase is a promising pharmacologic target to reverse unwanted immunosuppression.
Item Description:Prepublished online as Blood first edition paper, May 18, 2006
Gesehen am 09.11.2021
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2006-11-010389

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