Activated CD27PD-1 CD8 T Cells and CD4 T Regulatory Cells Dominate the Tumor Microenvironment in Refractory Celiac Disease Type II.

BACKGROUND AND AIMS

Refractory celiac disease type II (RCDII) is characterized by a clonally expanded aberrant cell population in the small intestine. The role of other tissue-resident immune subsets in RCDII is unknown. Here, we characterized CD8 and CD4 T cells in RCDII duodenum at the single-cell level and .

METHODS

We applied mass cytometry on CD45 duodenal cells derived from intestinal biopsies (n = 23) and blood samples (n = 20) from RCDII patients and controls. Additionally, we analyzed intestinal biopsies from celiac disease (n = 11) and RCDI (n = 2) patients. We performed single-cell RNA-sequencing on CD45 duodenal cells derived from a RCDII patient, immunofluorescence staining for analysis and flow cytometry for phenotyping of RCDII aberrant and CD8 T cells.

RESULTS

Compared to healthy controls, we observed that CD27PD-1 memory CD8αβ cells and CD4 T regulatories (Tregs) were more abundant in RCDII duodenum (CD8 ∗∗0.0029; CD4 ∗∗∗0.0001). The CD27PD-1 memory CD8αβ cells expressed the tissue-resident marker CD69, immunoregulatory markers (, NKG2A, were enriched for activated pathways and displayed cytotoxic gene signatures (. The absence of CD103 accords with their localization in the lamina propria as determined by analysis. The CD25FoxP3CD27CD127 CD4 Tregs expressed and and costimulatory molecules (, and ) and resided in the lamina propria as well. Flow cytometry confirmed the presence of the inhibitory receptor NKG2A on expanded duodenal CD8 T cells and HLA-E, the ligand for NKG2A, on expanded aberrant cells.

CONCLUSION

RCDII is characterized by the simultaneous presence of an activated CD27PD-1 memory CD8αβ T cell subset and CD4 Tregs, suggesting that checkpoint blockade with anti-NKG2A/PD-1 and/or anticytotoxic T lymphocyte antigen 4 may be an attractive treatment option.