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Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?

Whereas, neutrophils have long been considered to mainly function as efficient innate immunity killers of micro-organisms at infected sites, they are now recognized to also be involved in modulation of adaptive immune responses. Immature and mature neutrophils were reported to have the capacity to s...

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Autores principales: Aarts, Cathelijn E. M., Hiemstra, Ida H., Tool, Anton T. J., van den Berg, T. K., Mul, Erik, van Bruggen, Robin, Kuijpers, Taco W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749034/
https://www.ncbi.nlm.nih.gov/pubmed/31572368
http://dx.doi.org/10.3389/fimmu.2019.02144
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author Aarts, Cathelijn E. M.
Hiemstra, Ida H.
Tool, Anton T. J.
van den Berg, T. K.
Mul, Erik
van Bruggen, Robin
Kuijpers, Taco W.
author_facet Aarts, Cathelijn E. M.
Hiemstra, Ida H.
Tool, Anton T. J.
van den Berg, T. K.
Mul, Erik
van Bruggen, Robin
Kuijpers, Taco W.
author_sort Aarts, Cathelijn E. M.
collection PubMed
description Whereas, neutrophils have long been considered to mainly function as efficient innate immunity killers of micro-organisms at infected sites, they are now recognized to also be involved in modulation of adaptive immune responses. Immature and mature neutrophils were reported to have the capacity to suppress T cell-mediated immune responses as so-called granulocyte-myeloid-derived suppressor cells (g-MDSCs), and thereby affect the clinical outcome of cancer patients and impact the chronicity of microbial infections or rejection reactions in organ transplantation settings. These MDSCs were at first considered to be immature myeloid cells that left the bone marrow due to disease-specific signals. Current studies show that also mature neutrophils can exert suppressive activity. In this study we investigated in a robust T cell suppression assay whether immature CD11b+ myeloid cells were capable of MDSC activity comparable to mature fully differentiated neutrophils. We compared circulating neutrophils with myeloid cell fractions from the bone marrow at different differentiation stages. Our results indicate that functional MDSC activity is only becoming detectable at the final stage of differentiation, depending on the procedure of cell isolation. The MDSC activity obtained during neutrophil maturation correlated with the induction of the well-known highly mobile and toxic effector functions of the circulating neutrophil. Although immature neutrophils have been suggested to be increased in the circulation of cancer patients, we show here that immature neutrophils are not efficient in suppressing T cells. This suggests that the presence of immature neutrophils in the bloodstream of cancer patients represent a mere association or may function as a source of mature neutrophils in the tumor environment but not a direct cause of enhanced MDSC activity in cancer.
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spelling pubmed-67490342019-09-30 Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter? Aarts, Cathelijn E. M. Hiemstra, Ida H. Tool, Anton T. J. van den Berg, T. K. Mul, Erik van Bruggen, Robin Kuijpers, Taco W. Front Immunol Immunology Whereas, neutrophils have long been considered to mainly function as efficient innate immunity killers of micro-organisms at infected sites, they are now recognized to also be involved in modulation of adaptive immune responses. Immature and mature neutrophils were reported to have the capacity to suppress T cell-mediated immune responses as so-called granulocyte-myeloid-derived suppressor cells (g-MDSCs), and thereby affect the clinical outcome of cancer patients and impact the chronicity of microbial infections or rejection reactions in organ transplantation settings. These MDSCs were at first considered to be immature myeloid cells that left the bone marrow due to disease-specific signals. Current studies show that also mature neutrophils can exert suppressive activity. In this study we investigated in a robust T cell suppression assay whether immature CD11b+ myeloid cells were capable of MDSC activity comparable to mature fully differentiated neutrophils. We compared circulating neutrophils with myeloid cell fractions from the bone marrow at different differentiation stages. Our results indicate that functional MDSC activity is only becoming detectable at the final stage of differentiation, depending on the procedure of cell isolation. The MDSC activity obtained during neutrophil maturation correlated with the induction of the well-known highly mobile and toxic effector functions of the circulating neutrophil. Although immature neutrophils have been suggested to be increased in the circulation of cancer patients, we show here that immature neutrophils are not efficient in suppressing T cells. This suggests that the presence of immature neutrophils in the bloodstream of cancer patients represent a mere association or may function as a source of mature neutrophils in the tumor environment but not a direct cause of enhanced MDSC activity in cancer. Frontiers Media S.A. 2019-09-11 /pmc/articles/PMC6749034/ /pubmed/31572368 http://dx.doi.org/10.3389/fimmu.2019.02144 Text en Copyright © 2019 Aarts, Hiemstra, Tool, van den Berg, Mul, van Bruggen and Kuijpers. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Aarts, Cathelijn E. M.
Hiemstra, Ida H.
Tool, Anton T. J.
van den Berg, T. K.
Mul, Erik
van Bruggen, Robin
Kuijpers, Taco W.
Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?
title Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?
title_full Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?
title_fullStr Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?
title_full_unstemmed Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?
title_short Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?
title_sort neutrophils as suppressors of t cell proliferation: does age matter?
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749034/
https://www.ncbi.nlm.nih.gov/pubmed/31572368
http://dx.doi.org/10.3389/fimmu.2019.02144
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