Microvesicles released by apoptotic human neutrophils suppress proliferation and IL-2/IL-2 receptor expression of resting T helper cells

TY - JOUR

T1 - Microvesicles released by apoptotic human neutrophils suppress proliferation and IL-2/IL-2 receptor expression of resting T helper cells

AU - Shen, Guifen

AU - Krienke, Stefan

AU - Schiller, Petra

AU - Nießen, Anna

AU - Neu, Susanne

AU - Eckstein, Volker

AU - Schiller, Martin

AU - Lorenz, Hanns-Martin

AU - Tykocinski, Lars-Oliver

N1 - © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2017/5

Y1 - 2017/5

N2 - 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)neg CD127 (IL-7Rα)pos Th 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 CD25neg CD127pos Th 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.

AB - 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)neg CD127 (IL-7Rα)pos Th 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 CD25neg CD127pos Th 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.

KW - Apoptosis

KW - Cell Communication

KW - Cell Proliferation/drug effects

KW - Cell-Derived Microparticles/immunology

KW - Humans

KW - Immune Tolerance

KW - Interleukin-2/genetics

KW - Interleukin-2 Receptor alpha Subunit/genetics

KW - Interleukin-7/immunology

KW - Lymphocyte Activation/drug effects

KW - Neutrophils/immunology

KW - Signal Transduction

KW - T-Lymphocytes, Helper-Inducer/immunology

U2 - 10.1002/eji.201546203

DO - 10.1002/eji.201546203

M3 - SCORING: Journal article

C2 - 28295230

VL - 47

SP - 900

EP - 910

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 5

ER -