Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1.
Immunotherapy using regulatory T cells (Treg) has been proposed, yet cellular and molecular mechanisms of human Tregs remain incompletely characterized. Here, we demonstrate that human Tregs promote the generation of myeloid dendritic cells (DC) with reduced capacity to stimulate effector T cell res...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-02-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC2814822?pdf=render |
| _version_ | 1818690165685616640 |
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| author | Shoba Amarnath Carliann M Costanzo Jacopo Mariotti Jessica L Ullman William G Telford Veena Kapoor James L Riley Bruce L Levine Carl H June Timothy Fong Noel L Warner Daniel H Fowler |
| author_facet | Shoba Amarnath Carliann M Costanzo Jacopo Mariotti Jessica L Ullman William G Telford Veena Kapoor James L Riley Bruce L Levine Carl H June Timothy Fong Noel L Warner Daniel H Fowler |
| author_sort | Shoba Amarnath |
| collection | DOAJ |
| description | Immunotherapy using regulatory T cells (Treg) has been proposed, yet cellular and molecular mechanisms of human Tregs remain incompletely characterized. Here, we demonstrate that human Tregs promote the generation of myeloid dendritic cells (DC) with reduced capacity to stimulate effector T cell responses. In a model of xenogeneic graft-versus-host disease (GVHD), allogeneic human DC conditioned with Tregs suppressed human T cell activation and completely abrogated posttransplant lethality. Tregs induced programmed death ligand-1 (PD-L1) expression on Treg-conditioned DC; subsequently, Treg-conditioned DC induced PD-L1 expression in vivo on effector T cells. PD-L1 blockade reversed Treg-conditioned DC function in vitro and in vivo, thereby demonstrating that human Tregs can promote immune suppression via DC modulation through PD-L1 up-regulation. This identification of a human Treg downstream cellular effector (DC) and molecular mechanism (PD-L1) will facilitate the rational design of clinical trials to modulate alloreactivity. |
| first_indexed | 2024-12-17T12:21:40Z |
| format | Article |
| id | doaj.art-51447135cf054e8d9db8f38373ff2954 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-17T12:21:40Z |
| publishDate | 2010-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-51447135cf054e8d9db8f38373ff29542022-12-21T21:48:57ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852010-02-0182e100030210.1371/journal.pbio.1000302Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1.Shoba AmarnathCarliann M CostanzoJacopo MariottiJessica L UllmanWilliam G TelfordVeena KapoorJames L RileyBruce L LevineCarl H JuneTimothy FongNoel L WarnerDaniel H FowlerImmunotherapy using regulatory T cells (Treg) has been proposed, yet cellular and molecular mechanisms of human Tregs remain incompletely characterized. Here, we demonstrate that human Tregs promote the generation of myeloid dendritic cells (DC) with reduced capacity to stimulate effector T cell responses. In a model of xenogeneic graft-versus-host disease (GVHD), allogeneic human DC conditioned with Tregs suppressed human T cell activation and completely abrogated posttransplant lethality. Tregs induced programmed death ligand-1 (PD-L1) expression on Treg-conditioned DC; subsequently, Treg-conditioned DC induced PD-L1 expression in vivo on effector T cells. PD-L1 blockade reversed Treg-conditioned DC function in vitro and in vivo, thereby demonstrating that human Tregs can promote immune suppression via DC modulation through PD-L1 up-regulation. This identification of a human Treg downstream cellular effector (DC) and molecular mechanism (PD-L1) will facilitate the rational design of clinical trials to modulate alloreactivity.http://europepmc.org/articles/PMC2814822?pdf=render |
| spellingShingle | Shoba Amarnath Carliann M Costanzo Jacopo Mariotti Jessica L Ullman William G Telford Veena Kapoor James L Riley Bruce L Levine Carl H June Timothy Fong Noel L Warner Daniel H Fowler Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1. PLoS Biology |
| title | Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1. |
| title_full | Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1. |
| title_fullStr | Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1. |
| title_full_unstemmed | Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1. |
| title_short | Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1. |
| title_sort | regulatory t cells and human myeloid dendritic cells promote tolerance via programmed death ligand 1 |
| url | http://europepmc.org/articles/PMC2814822?pdf=render |
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