In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 4 ( 2021-4-26), p. e3001199-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001199
DOI:
10.1371/journal.pbio.3001199.g001
DOI:
10.1371/journal.pbio.3001199.g002
DOI:
10.1371/journal.pbio.3001199.g003
DOI:
10.1371/journal.pbio.3001199.g004
DOI:
10.1371/journal.pbio.3001199.g005
DOI:
10.1371/journal.pbio.3001199.g006
DOI:
10.1371/journal.pbio.3001199.g007
DOI:
10.1371/journal.pbio.3001199.g008
DOI:
10.1371/journal.pbio.3001199.s001
DOI:
10.1371/journal.pbio.3001199.s002
DOI:
10.1371/journal.pbio.3001199.s003
DOI:
10.1371/journal.pbio.3001199.s004
DOI:
10.1371/journal.pbio.3001199.s005
DOI:
10.1371/journal.pbio.3001199.s006
DOI:
10.1371/journal.pbio.3001199.s007
DOI:
10.1371/journal.pbio.3001199.s008
DOI:
10.1371/journal.pbio.3001199.s009
DOI:
10.1371/journal.pbio.3001199.s010
DOI:
10.1371/journal.pbio.3001199.s011
DOI:
10.1371/journal.pbio.3001199.s012
DOI:
10.1371/journal.pbio.3001199.s013
DOI:
10.1371/journal.pbio.3001199.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
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