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Human Endothelial Cells Modulate CD4(+) T Cell Populations and Enhance Regulatory
T Cell Suppressive Capacity
#MMPMID29628925
Lim WC
; Olding M
; Healy E
; Millar TM
Front Immunol
2018[]; 9
(?): 565
PMID29628925
show ga
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-?
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.
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