PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype.
Programmed cell death protein 1 (PD-1) is expressed on T cells upon T cell receptor (TCR) stimulation. PD-1 ligand 1 (PD-L1) is expressed in most tumor environments, and its binding to PD-1 on T cells drives them to apoptosis or into a regulatory phenotype. The fact that PD-L1 itself is also express...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-04-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001199&type=printable |
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| author | Giorgia Fanelli Marco Romano Estefania Nova-Lamperti Mariana Werner Sunderland Alessandra Nerviani Cristiano Scottà Michele Bombardieri Sergio A Quezada Steven H Sacks Randolph J Noelle Costantino Pitzalis Robert I Lechler Giovanna Lombardi Pablo D Becker |
| author_facet | Giorgia Fanelli Marco Romano Estefania Nova-Lamperti Mariana Werner Sunderland Alessandra Nerviani Cristiano Scottà Michele Bombardieri Sergio A Quezada Steven H Sacks Randolph J Noelle Costantino Pitzalis Robert I Lechler Giovanna Lombardi Pablo D Becker |
| author_sort | Giorgia Fanelli |
| collection | DOAJ |
| description | Programmed cell death protein 1 (PD-1) is expressed on T cells upon T cell receptor (TCR) stimulation. PD-1 ligand 1 (PD-L1) is expressed in most tumor environments, and its binding to PD-1 on T cells drives them to apoptosis or into a regulatory phenotype. The fact that PD-L1 itself is also expressed on T cells upon activation has been largely neglected. Here, we demonstrate that PD-L1 ligation on human CD25-depleted CD4+ T cells, combined with CD3/TCR stimulation, induces their conversion into highly suppressive T cells. Furthermore, this effect was most prominent in memory (CD45RA-CD45RO+) T cells. PD-L1 engagement on T cells resulted in reduced ERK phosphorylation and decreased AKT/mTOR/S6 signaling. Importantly, T cells from rheumatoid arthritis patients exhibited high basal levels of phosphorylated ERK and following PD-L1 cross-linking both ERK signaling and the AKT/mTOR/S6 pathway failed to be down modulated, making them refractory to the acquisition of a regulatory phenotype. Altogether, our results suggest that PD-L1 signaling on memory T cells could play an important role in resolving inflammatory responses; maintaining a tolerogenic environment and its failure could contribute to ongoing autoimmunity. |
| format | Article |
| id | doaj-art-3fbd2067f1594e26aba21fe040a73129 |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2021-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-3fbd2067f1594e26aba21fe040a731292025-08-20T02:23:08ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-04-01194e300119910.1371/journal.pbio.3001199PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype.Giorgia FanelliMarco RomanoEstefania Nova-LampertiMariana Werner SunderlandAlessandra NervianiCristiano ScottàMichele BombardieriSergio A QuezadaSteven H SacksRandolph J NoelleCostantino PitzalisRobert I LechlerGiovanna LombardiPablo D BeckerProgrammed cell death protein 1 (PD-1) is expressed on T cells upon T cell receptor (TCR) stimulation. PD-1 ligand 1 (PD-L1) is expressed in most tumor environments, and its binding to PD-1 on T cells drives them to apoptosis or into a regulatory phenotype. The fact that PD-L1 itself is also expressed on T cells upon activation has been largely neglected. Here, we demonstrate that PD-L1 ligation on human CD25-depleted CD4+ T cells, combined with CD3/TCR stimulation, induces their conversion into highly suppressive T cells. Furthermore, this effect was most prominent in memory (CD45RA-CD45RO+) T cells. PD-L1 engagement on T cells resulted in reduced ERK phosphorylation and decreased AKT/mTOR/S6 signaling. Importantly, T cells from rheumatoid arthritis patients exhibited high basal levels of phosphorylated ERK and following PD-L1 cross-linking both ERK signaling and the AKT/mTOR/S6 pathway failed to be down modulated, making them refractory to the acquisition of a regulatory phenotype. Altogether, our results suggest that PD-L1 signaling on memory T cells could play an important role in resolving inflammatory responses; maintaining a tolerogenic environment and its failure could contribute to ongoing autoimmunity.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001199&type=printable |
| spellingShingle | Giorgia Fanelli Marco Romano Estefania Nova-Lamperti Mariana Werner Sunderland Alessandra Nerviani Cristiano Scottà Michele Bombardieri Sergio A Quezada Steven H Sacks Randolph J Noelle Costantino Pitzalis Robert I Lechler Giovanna Lombardi Pablo D Becker PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. PLoS Biology |
| title | PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. |
| title_full | PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. |
| title_fullStr | PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. |
| title_full_unstemmed | PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. |
| title_short | PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. |
| title_sort | pd l1 signaling on human memory cd4 t cells induces a regulatory phenotype |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001199&type=printable |
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