Galletti, Giovanni and De Simone, Gabriele and Mazza, Emilia M. C. and Puccio, Simone and Mezzanotte, Claudia and Bi, Timothy M. and Davydov, Alexey N. and Metsger, Maria and Scamardella, Eloise and Alvisi, Giorgia and De Paoli, Federica and Zanon, Veronica and Scarpa, Alice and Camisa, Barbara and Colombo, Federico S. and Anselmo, Achille and Peano, Clelia and Polletti, Sara and Mavilio, Domenico and Gattinoni, Luca and Boi, Shannon K. and Youngblood, Benjamin A. and Jones, Rhiannon E. and Baird, Duncan M. and Gostick, Emma and Llewellyn-Lacey, Sian and Ladell, Kristin and Price, David A. and Chudakov, Dmitriy M. and Newell, Evan W. and Casucci, Monica and Lugli, Enrico (2020) Two subsets of stem-like CD8(+)memory T cell progenitors with distinct fate commitments in humans. NATURE IMMUNOLOGY, 21 (12). 1552-+. ISSN 1529-2908, 1529-2916
Full text not available from this repository. (Request a copy)Abstract
The identity of stem-cell memory progenitor cells has been unclear. Lugli and colleagues use high-dimensional approaches to identify two new progenitor populations of human T cells-one giving rise to a functional lineage, the other to an exhausted-like one. T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8(+)memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8(+)memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8(+)memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIFFERENTIATION; EXHAUSTION; EFFECTOR; EXPRESSION; STATES; PD-1; RECONSTITUTION; DYSFUNCTION; INFECTION; CHROMATIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2021 06:42 |
| Last Modified: | 09 Mar 2021 06:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43572 |
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