Article ; Online: PD-1 Limits IL-2 Production and Thymic Regulatory T Cell Development.
ImmunoHorizons
2024 Volume 8, Issue 3, Page(s) 281–294
Abstract: Inhibitory proteins, such as programmed cell death protein 1 (PD-1), have been studied extensively in peripheral T cell responses to foreign Ags, self-Ags, and neoantigens. Notably, these proteins are first expressed during T cell development in the ... ...
Abstract | Inhibitory proteins, such as programmed cell death protein 1 (PD-1), have been studied extensively in peripheral T cell responses to foreign Ags, self-Ags, and neoantigens. Notably, these proteins are first expressed during T cell development in the thymus. Reports suggest that PD-1 limits regulatory T cell (Treg) development, but the mechanism by which PD-1 exerts this function remains unknown. The present study expands the evaluation of murine PD-1 and its ligands in the thymus, demonstrating that some of the highest expressers of PD-1 and programmed death-ligand 1 are agonist selected cells. Surprisingly, we reveal a selective role for PD-1 in regulating the developmental niche only for Tregs because other agonist selected cell populations, such as NK T cells, remain unchanged. We also ruled out PD-1 as a regulator of proliferation or cell death of agonist selected Tregs and further demonstrated that PD-1-deficient Tregs have reduced TCR signaling. Unexpectedly, the data suggest that PD-1-deficient thymocytes produce elevated levels of IL-2, a Treg niche-limiting cytokine. Collectively, these data suggest a novel role for PD-1 in regulating IL-2 production and the concurrent agonist selection of murine thymic Tregs. This observation has implications for the use of checkpoint blockade in the context of cancer and infection. |
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MeSH term(s) | Animals ; Mice ; Cytokines/metabolism ; Interleukin-2/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; T-Lymphocytes, Regulatory/immunology ; Thymus Gland/cytology ; Thymus Gland/immunology |
Chemical Substances | Cytokines ; Interleukin-2 ; Programmed Cell Death 1 Receptor ; Pdcd1 protein, mouse |
Language | English |
Publishing date | 2024-03-29 |
Publishing country | United States |
Document type | Journal Article |
ISSN | 2573-7732 |
ISSN (online) | 2573-7732 |
DOI | 10.4049/immunohorizons.2300079 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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