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J Exp Med. 2019 Jul 23. pii: jem.20190414. doi: 10.1084/jem.20190414. [Epub ahead of print]

Resident memory CD8 T cells persist for years in human small intestine.

Author information

1
Department of Pathology, Oslo University Hospital and University of Oslo, Oslo, Norway r.b.casado@medisin.uio.no.
2
Department of Pathology, Oslo University Hospital and University of Oslo, Oslo, Norway.
3
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
4
Core Facility Flow Cytometry, Biomedical Center, Ludwig-Maximilians-University Munich, Munich, Germany.
5
Department of Immunology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
6
Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
7
K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
8
Department of Gastrointestinal Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
9
Department of Transplantation Medicine, Section for Transplant Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
10
Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
11
Department of Pathology, Oslo University Hospital and University of Oslo, Oslo, Norway f.l.jahnsen@medisin.uio.no.

Abstract

Resident memory CD8 T (Trm) cells have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI, we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for >1 yr in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.

PMID:
31337737
DOI:
10.1084/jem.20190414

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