Cargando…
Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity
Endothelial cells (ECs) line the luminal surface of blood vessels and have an active role in the recruitment of leukocytes, including immune cell activation. Regulatory T cells (Tregs) are immune suppressor cells that maintain peripheral tolerance and must interact with the endothelium as they traff...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876242/ https://www.ncbi.nlm.nih.gov/pubmed/29628925 http://dx.doi.org/10.3389/fimmu.2018.00565 |
_version_ | 1783310469319098368 |
---|---|
author | Lim, Wen Chean Olding, Michael Healy, Eugene Millar, Timothy M. |
author_facet | Lim, Wen Chean Olding, Michael Healy, Eugene Millar, Timothy M. |
author_sort | Lim, Wen Chean |
collection | PubMed |
description | Endothelial cells (ECs) line the luminal surface of blood vessels and have an active role in the recruitment of leukocytes, including immune cell activation. Regulatory T cells (Tregs) are immune suppressor cells that maintain peripheral tolerance and must interact with the endothelium as they traffic into tissue. We hypothesized that human ECs could modulate Tregs and their suppressor function. Cocultures of CD4(+) T cells with human umbilical vein ECs (HUVECs) or dermal microvascular ECs (HDMECs) were conducted and analyzed for activation and proliferation after 72 and 120 h using flow cytometry. In monocyte-depleted cultures, human ECs were found to support CD4(+) T cell proliferation in the presence of external mitogens phytohemagglutinin or anti-CD3/28 antibodies (aCD3/28). Activation was shown by CD25 expression in these cells that also transiently expressed the Treg transcription factor FOXP3. HUVECs supported the specific concurrent proliferation of both effector T cells and Tregs when cocultured with aCD3/28. Purified Tregs were also functionally activated by prior coculture with EC to suppress effector T (Teff) cell proliferation. Both direct coculture and indirect coculture of EC and Treg showed activation of the Treg suppressive phenotype. However, whereas HUVEC showed enhancement of suppression by both mechanisms, HDMEC only supported Treg suppressive activity via the contact-independent mechanism. In the contact-independent cultures, the soluble mediators IL-6, GM-CSF, or G-CSF released from ECs following interferon-γ activation were not responsible for the enhanced Treg suppressor function. Following direct coculture, Treg expression of inhibitory receptors PD-1 and OX40 was elevated while activated EC expressed the counter ligands programmed death ligand (PD-L)1 and PD-L2. Therefore, human ECs have a role in supporting T cell proliferation and increasing Treg suppressor function. This ability of EC to enhance Treg function could offer novel targets to boost Treg activity during inflammatory disorders. |
format | Online Article Text |
id | pubmed-5876242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58762422018-04-06 Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity Lim, Wen Chean Olding, Michael Healy, Eugene Millar, Timothy M. Front Immunol Immunology Endothelial cells (ECs) line the luminal surface of blood vessels and have an active role in the recruitment of leukocytes, including immune cell activation. Regulatory T cells (Tregs) are immune suppressor cells that maintain peripheral tolerance and must interact with the endothelium as they traffic into tissue. We hypothesized that human ECs could modulate Tregs and their suppressor function. Cocultures of CD4(+) T cells with human umbilical vein ECs (HUVECs) or dermal microvascular ECs (HDMECs) were conducted and analyzed for activation and proliferation after 72 and 120 h using flow cytometry. In monocyte-depleted cultures, human ECs were found to support CD4(+) T cell proliferation in the presence of external mitogens phytohemagglutinin or anti-CD3/28 antibodies (aCD3/28). Activation was shown by CD25 expression in these cells that also transiently expressed the Treg transcription factor FOXP3. HUVECs supported the specific concurrent proliferation of both effector T cells and Tregs when cocultured with aCD3/28. Purified Tregs were also functionally activated by prior coculture with EC to suppress effector T (Teff) cell proliferation. Both direct coculture and indirect coculture of EC and Treg showed activation of the Treg suppressive phenotype. However, whereas HUVEC showed enhancement of suppression by both mechanisms, HDMEC only supported Treg suppressive activity via the contact-independent mechanism. In the contact-independent cultures, the soluble mediators IL-6, GM-CSF, or G-CSF released from ECs following interferon-γ activation were not responsible for the enhanced Treg suppressor function. Following direct coculture, Treg expression of inhibitory receptors PD-1 and OX40 was elevated while activated EC expressed the counter ligands programmed death ligand (PD-L)1 and PD-L2. Therefore, human ECs have a role in supporting T cell proliferation and increasing Treg suppressor function. This ability of EC to enhance Treg function could offer novel targets to boost Treg activity during inflammatory disorders. Frontiers Media S.A. 2018-03-23 /pmc/articles/PMC5876242/ /pubmed/29628925 http://dx.doi.org/10.3389/fimmu.2018.00565 Text en Copyright © 2018 Lim, Olding, Healy and Millar. https://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 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 Lim, Wen Chean Olding, Michael Healy, Eugene Millar, Timothy M. Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity |
title | Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity |
title_full | Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity |
title_fullStr | Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity |
title_full_unstemmed | Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity |
title_short | Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory T Cell Suppressive Capacity |
title_sort | human endothelial cells modulate cd4(+) t cell populations and enhance regulatory t cell suppressive capacity |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876242/ https://www.ncbi.nlm.nih.gov/pubmed/29628925 http://dx.doi.org/10.3389/fimmu.2018.00565 |
work_keys_str_mv | AT limwenchean humanendothelialcellsmodulatecd4tcellpopulationsandenhanceregulatorytcellsuppressivecapacity AT oldingmichael humanendothelialcellsmodulatecd4tcellpopulationsandenhanceregulatorytcellsuppressivecapacity AT healyeugene humanendothelialcellsmodulatecd4tcellpopulationsandenhanceregulatorytcellsuppressivecapacity AT millartimothym humanendothelialcellsmodulatecd4tcellpopulationsandenhanceregulatorytcellsuppressivecapacity |