Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 216, Issue 10, Pages 2412-2426Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20190414
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- Research Council of Norway [179573/V40]
- South Eastern Norway Regional Health Authority [2015002]
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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-gamma(+) IL-2(+) TNF-alpha(+)) 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.
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