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PD-1-stimulated T cell subsets are transcriptionally and functionally distinct.

ABSTRACT: Despite the obvious inhibitory outcome of PD-1 signaling, an additional series of functions are activated. We have observed that T cells stimulated through the T cell receptor (TCR) and PD-1 primarily do not proliferate; however, there is a population of cells that proliferates more than through TCR stimulation alone. In this study, we performed flow cytometry and RNA sequencing on individual populations of T cells and discovered that unlike naive T cells, which were inhibited following PD-1 ligation, T cells that proliferated more following PD-1 ligation were associated with effector and central memory phenotypes. We showed that these populations had different gene expression profiles following PD-1 ligation with PD-L1 compared to PD-L2. The presence of transcriptionally and functionally distinct T cell populations responsive to PD-1 ligation provides new insights into the biology of PD-1 and suggest the use of T cell subset-specific approaches to improve the clinical outcome of PD-1 blockade.

SUBMITTER: Lerrer S

PROVIDER: S-EPMC8426269 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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PD-1-stimulated T cell subsets are transcriptionally and functionally distinct.

Lerrer Shalom S Tocheva Anna S AS Bukhari Shoiab S Adam Kieran K Mor Adam A

iScience 20210824 9

Despite the obvious inhibitory outcome of PD-1 signaling, an additional series of functions are activated. We have observed that T cells stimulated through the T cell receptor (TCR) and PD-1 primarily do not proliferate; however, there is a population of cells that proliferates more than through TCR stimulation alone. In this study, we performed flow cytometry and RNA sequencing on individual populations of T cells and discovered that unlike naive T cells, which were inhibited following PD-1 lig ...[more]

PMID: 34522863

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