title: Microvesicles released by apoptotic human neutrophils suppress proliferation and IL-2/IL-2 receptor expression of resting T helper cells.
abstract: Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likely that they are the source of large amounts of apoptotic cell-derived MVs. Here, we show that MVs released by apoptotic human polymorphonuclear neutrophils (apoPMN-MVs), but not the apoptotic neutrophils themselves, selectively suppress the proliferation of CD25 (IL-2Rα)negCD127 (IL-7Rα)posTh cells in a dose-dependent manner. In contrast, the proliferation of total T cells is not affected by MVs. Importantly, apoPMN-MVs suppress the secretion of IL-2 as well as the expression of and signaling via the IL-2 receptor (IL-2R) by CD25negCD127posTh cells. Addition of IL-7 strongly reduced the suppression of T-cell proliferation by MVs and the addition of IL-2 completely abrogated the suppressive effect. Thus, apoPMN-MVs suppressed a subset of Th cells by downregulating IL-2 and IL-2R expression and signaling. This may represent an important mechanism to prevent the activation and expansion of resting T cells in the absence of sufficient cytokine stimulation, and thereby maintaining immune tolerance.
authors.affiliation: Division of Rheumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guifen
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Krienke
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Schiller
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Nießen
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Neu
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schiller
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.|ACURA Center for Rheumatic Diseases, Baden-Baden, Germany.
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Lars-Oliver
authors.identifier: 0000-0002-7645-1559
authors.initials: LO
authors.lastname: Tykocinski
mesh_terms: D017209:Apoptosis; D002450:Cell Communication; D049109:Cell Proliferation / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000502:physiology
chemical_list: C508017:IL2RA protein, human; C508605:IL7 protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7
keywords: Apoptosis; Cell death; Extracellular vesicles; Microvesicles; Neutrophils; T cells