Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes
Endothelial cells (ECs) can present antigens to circulating effector memory T cells (TEM) and to regulatory T cells (T regs), triggering antigen-specific extravasation at specific sites where foreign antigens are introduced, e.g. by infection or transplantation. We model human antigen-induced transe...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016361/full |
| _version_ | 1811229089010286592 |
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| author | Thomas D. Manes Vivian Wang Jordan S. Pober |
| author_facet | Thomas D. Manes Vivian Wang Jordan S. Pober |
| author_sort | Thomas D. Manes |
| collection | DOAJ |
| description | Endothelial cells (ECs) can present antigens to circulating effector memory T cells (TEM) and to regulatory T cells (T regs), triggering antigen-specific extravasation at specific sites where foreign antigens are introduced, e.g. by infection or transplantation. We model human antigen-induced transendothelial migration (TEM) using presentation of superantigen by cultured human dermal microvascular (HDM)ECs to isolated resting human peripheral blood T cell subpopulations or to T effector cells activated in vitro. T cell receptor (TCR)-mediated cytokine synthesis, a common assay of T cell activation by antigen, is modulated by antigen-independent signals provided by various positive or negative costimulator proteins (the latter known as checkpoint inhibitors) expressed by antigen presenting cells, including ECs. We report here that some EC-expressed costimulators also modulate TCR-TEM, but effects differ between TEM and cytokine production and among some T cell types. Blocking EC LFA-3 interactions with TEM CD2 boosts TEM but reduces cytokine production. Blocking EC ICOS-L interactions with TEM CD28 (but not ICOS) reduces both responses but these involve distinct CD28-induced signals. Activated CD4+ T effector cells no longer undergo TCR-TEM. Engagement of T cell CD28 by EC ICOS-L increases TCR-TEM by activated CD8 effectors while engagement of OX40 promotes TCR-TEM by activated CD4 T regs. B7-H3 mostly affects TEM of resting TEM and some checkpoint inhibitors affect cytokine synthesis or TEM depending upon subtype. Our data suggest that blockade or mimicry of costimulators/checkpoint inhibitors in vivo, clinically used to modulate immune responses, may act in part by modulating T cell homing. |
| first_indexed | 2024-04-12T10:08:38Z |
| format | Article |
| id | doaj.art-3a585cf46dec486083f0faa340f7c926 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T10:08:38Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3a585cf46dec486083f0faa340f7c9262022-12-22T03:37:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10163611016361Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytesThomas D. ManesVivian WangJordan S. PoberEndothelial cells (ECs) can present antigens to circulating effector memory T cells (TEM) and to regulatory T cells (T regs), triggering antigen-specific extravasation at specific sites where foreign antigens are introduced, e.g. by infection or transplantation. We model human antigen-induced transendothelial migration (TEM) using presentation of superantigen by cultured human dermal microvascular (HDM)ECs to isolated resting human peripheral blood T cell subpopulations or to T effector cells activated in vitro. T cell receptor (TCR)-mediated cytokine synthesis, a common assay of T cell activation by antigen, is modulated by antigen-independent signals provided by various positive or negative costimulator proteins (the latter known as checkpoint inhibitors) expressed by antigen presenting cells, including ECs. We report here that some EC-expressed costimulators also modulate TCR-TEM, but effects differ between TEM and cytokine production and among some T cell types. Blocking EC LFA-3 interactions with TEM CD2 boosts TEM but reduces cytokine production. Blocking EC ICOS-L interactions with TEM CD28 (but not ICOS) reduces both responses but these involve distinct CD28-induced signals. Activated CD4+ T effector cells no longer undergo TCR-TEM. Engagement of T cell CD28 by EC ICOS-L increases TCR-TEM by activated CD8 effectors while engagement of OX40 promotes TCR-TEM by activated CD4 T regs. B7-H3 mostly affects TEM of resting TEM and some checkpoint inhibitors affect cytokine synthesis or TEM depending upon subtype. Our data suggest that blockade or mimicry of costimulators/checkpoint inhibitors in vivo, clinically used to modulate immune responses, may act in part by modulating T cell homing.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016361/fullT celltransendothelial and transepithelial migrationcostimulating moleculescytokine expressionflow chamber assay |
| spellingShingle | Thomas D. Manes Vivian Wang Jordan S. Pober Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes Frontiers in Immunology T cell transendothelial and transepithelial migration costimulating molecules cytokine expression flow chamber assay |
| title | Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes |
| title_full | Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes |
| title_fullStr | Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes |
| title_full_unstemmed | Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes |
| title_short | Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes |
| title_sort | costimulators expressed on human endothelial cells modulate antigen dependent recruitment of circulating t lymphocytes |
| topic | T cell transendothelial and transepithelial migration costimulating molecules cytokine expression flow chamber assay |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016361/full |
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