| Autor: |
Bennion, Kelsey B., Liu, Danya, Dawood, Abdelhameed S., Wyatt, Megan M., Alexander, Katie L., Abdel-Hakeem, Mohamed S., Paulos, Chrystal M., Ford, Mandy L. |
| Předmět: |
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| Zdroj: |
Nature Communications; 6/20/2024, Vol. 15 Issue 1, p1-15, 15p |
| Abstrakt: |
The regulatory circuits dictating CD8+ T cell responsiveness versus exhaustion during anti-tumor immunity are incompletely understood. Here we report that tumor-infiltrating antigen-specific PD-1+ TCF-1− CD8+ T cells express the immunosuppressive cytokine Fgl2. Conditional deletion of Fgl2 specifically in mouse antigen-specific CD8+ T cells prolongs CD8+ T cell persistence, suppresses phenotypic and transcriptomic signatures of T cell exhaustion, and improves control of the tumor. In a mouse model of chronic viral infection, PD-1+ CD8+ T cell-derived Fgl2 also negatively regulates virus-specific T cell responses. In humans, CD8+ T cell-derived Fgl2 is associated with poorer survival in patients with melanoma. Mechanistically, the dampened responsiveness of WT Fgl2-expressing CD8+ T cells, when compared to Fgl2-deficient CD8+ T cells, is underpinned by the cell-intrinsic interaction of Fgl2 with CD8+ T cell-expressed FcγRIIB and concomitant caspase 3/7-mediated apoptosis. Our results thus illuminate a cell-autonomous regulatory axis by which PD-1+ CD8+ T cells both express the receptor and secrete its ligand in order to mediate suppression of anti-tumor and anti-viral immunity. Mechanisms regulating CD8 T cell responsiveness are not fully understood. Here the authors show, using mouse genetic tools and human patient samples, that CD8 T-derived Fgl2, an immunosuppressive cytokine, binds autologous FcγRIIB receptor to induce CD8 T cell apoptosis and dampen anti-tumor or antivirus immunity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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