title: Suppression of T-cell functions by human granulocyte arginase.
abstract: 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 CD3zeta 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.
authors.affiliation: Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. markus_munder@med.uni-heidelberg.de
authors.forename: Markus
authors.initials: M
authors.lastname: Munder
authors.forename: Henriette
authors.initials: H
authors.lastname: Schneider
authors.forename: Claudia
authors.initials: C
authors.lastname: Luckner
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Langhans
authors.forename: Jose M
authors.initials: JM
authors.lastname: Fuentes
authors.forename: Pascale
authors.initials: P
authors.lastname: Kropf
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mueller
authors.forename: Armin
authors.initials: A
authors.lastname: Kolb
authors.forename: Manuel
authors.initials: M
authors.lastname: Modolell
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
mesh_terms: D001119:Arginase / Q000235:genetics / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism; D006098:Granulocytes / Q000201:enzymology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D001120:Arginine; D001119:Arginase