Format

Send to

Choose Destination
Science. 2019 Oct 11;366(6462). pii: eaav5728. doi: 10.1126/science.aav5728.

Migratory DCs activate TGF-β to precondition naïve CD8+ T cells for tissue-resident memory fate.

Author information

1
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
2
Immunology Graduate Program, Harvard Medical School, Boston, MA, USA.
3
Harvard Medical School, Boston, MA, USA.
4
Center for Computational Biology, Flatiron Institute, New York, NY, USA.
5
Bluebird Bio, 60 Binney Street, Cambridge, MA 02142, USA.
6
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
7
Benaroya Research Institute, Seattle, WA, USA.
8
Lydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
9
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA.
10
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA. tmempel@mgh.harvard.edu.

Abstract

Epithelial resident memory T (eTRM) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eTRM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8+ T cells and prepares them for the formation of eTRM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I-dependent interactions with peripheral tissue-derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β-activating αV integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.

Comment in

PMID:
31601741
DOI:
10.1126/science.aav5728

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center