title: A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.
abstract: Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transplantation, and autoimmune disease. Here, we report the identification of a subset of mature human neutrophils (CD11cbright/CD62Ldim/CD11bbright/CD16bright) as what we believe to be a unique circulating population of myeloid cells, capable of suppressing human T cell proliferation. These cells were observed in humans in vivo during acute systemic inflammation induced by endotoxin challenge or by severe injury. Local release of hydrogen peroxide from the neutrophils into the immunological synapse between the neutrophils and T cells mediated the suppression of T cell proliferation and required neutrophil expression of the integrin Mac-1 (αMβ2). Our data demonstrate that suppression of T cell function can be accomplished by a subset of human neutrophils that can be systemically induced in response to acute inflammation. Identification of the pivotal role of neutrophil Mac-1 and ROS in this process provides a potential target for modulating immune responses in humans.
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Janesh
authors.initials: J
authors.lastname: Pillay
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kamp
authors.forename: Els
authors.initials: E
authors.lastname: van Hoffen
authors.forename: Tjaakje
authors.initials: T
authors.lastname: Visser
authors.forename: Tamar
authors.initials: T
authors.lastname: Tak
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Lammers
authors.forename: Laurien H
authors.initials: LH
authors.lastname: Ulfman
authors.forename: Luke P
authors.initials: LP
authors.lastname: Leenen
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D006801:Humans; D007108:Immune Tolerance; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009504:Neutrophils / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D017382:Reactive Oxygen Species