Publication details
Two subsets of stem-like CD8(+)memory T cell progenitors with distinct fate commitments in humans
| Authors | |
|---|---|
| Year of publication | 2020 |
| Type | Article in Periodical |
| Magazine / Source | Nature immunology |
| MU Faculty or unit | |
| Citation | |
| Web | https://www.nature.com/articles/s41590-020-0791-5 |
| Doi | http://dx.doi.org/10.1038/s41590-020-0791-5 |
| Keywords | DIFFERENTIATION; EXHAUSTION; EFFECTOR; EXPRESSION; STATES; PD-1; RECONSTITUTION; DYSFUNCTION; INFECTION; CHROMATIN |
| Description | 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. |
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