Jahnsen, F. L. | bioRxiv Science

bioRxiv2019

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

In human small intestine, most CD8 T cells in the lamina propria and epithelium express a resident memory (Trm) phenotype and persist for at least one year in transplanted tissue. Intestinal CD8 Trm cells have a clonally expanded immune repertoire that is stable over time and exhibit enhanced protective capabilities. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/553792v1_ufig1.gif" ALT="Figure 1"> View larger version (98K): org.highwire.dtl.DTLVardef@10c19aaorg.highwire.dtl.DTLVardef@168e86forg.highwire.dtl.DTLVardef@73f0f5org.highwire.dtl.DTLVardef@1d08d10_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe vast majority of CD8 T cells in the human small intestine are Trm cells C_LIO_LICD8 Trm cells persist for >1 year in transplanted duodenum C_LIO_LIIntraepithelial and lamina propria CD8 Trm cells show highly similar TCR repertoire C_LIO_LIIntestinal CD8 Trm cells efficiently produce cytokines and cytotoxic mediators C_LI

immunology↗

bioRxiv2018

Characterization of the endocrine pancreas in Type 1 Diabetes: islet size is maintained but islet number is markedly reduced

Insulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of specific beta-cell loss. Since healthy pancreatic islets consist of ~65% beta cells, this would lead to reduced islet size if the beta cells are not replaced by other cells or tissue. The number of islets per pancreas volume (islet density) would not be affected.\n\nIn this study, we compared the islet density, size, and size distribution in subjects with recent-onset or long-standing T1D, with that in matched non-diabetic subjects. Results show that subjects with T1D, regardless of disease duration, had a dramatically reduced islet number per mm2, while the islet size was similar in all groups. Insulin-negative islets in T1D subjects were dominated by glucagon-positive cells that frequently had lost the alpha-cell transcription factor ARX while instead expressing PDX1, normally expressed in beta cells.\n\nBased on our findings, we propose that failure during childhood to establish a sufficient islet number to reach the beta-cell mass needed to cope with episodes of increased insulin demand contributes to T1D susceptibility. Exhaustion induced by relative lack of beta cells could then potentially drive beta-cell dedifferentiation to alpha-cells, explaining the preserved islet size observed in T1D compared to controls.

pathology↗