Decreased Frequency of Intestinal CD39+ γδ+ T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease

Abstract

The ectoenzymes CD39 and CD73 play a major role in controlling tissue inflammation by regulating the balance between adenosine triphosphate (ATP) and adenosine. Still, little is known about the role of these two enzymes and ATP and its metabolites in the pathophysiology of inflammatory bowel disease (IBD). We isolated mononuclear cells from peripheral blood and lamina propria of the large intestine of patients diagnosed with IBD and of healthy volunteers. We then comprehensively analyzed the CD39 and CD73 expression patterns together with markers of activation (HLA-DR, CD38), differentiation (CCR7, CD45RA) and tissue-residency (CD69, CD103, CD49a) on CD4 + , CD8 + , γδ + T cells and mucosa-associated invariant T cells using flow cytometry. CD39 expression levels of γδ + and CD8 + T cells in lamina propria lymphocytes (LPL) were much higher compared to peripheral blood mononuclear cells. Moreover, the frequency of CD39 + CD4 + and CD8 + , but not γδ + LPL positively correlated with T-cell activation. The frequency of CD39 + cells among tissue-resident memory LPL (Trm) was higher compared to non-Trm for all subsets, confirming that CD39 is a marker for the tissueresident memory phenotype. γδ + Trm also showed a distinct cytokine profile upon stimulation-the frequency of IFN-γ + and IL-17A + cells was significantly lower in γδ + Trm compared to non-Trm. Interestingly, we observed a decreased frequency of CD39 + γδ + T cells in IBD patients compared to healthy controls (p = 0.0049). Prospective studies need to elucidate the exact role of this novel CD39 + γδ + T-cell population with tissue-resident memory phenotype and its possible contribution to the pathogenesis of IBD and other inflammatory disorders.

Bone Marrow-Resident Vδ1 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma

“…CD39 + expression has been reported on tissue-resident γδ T cells ( 64 ). Moreover, CD39 + γδ T cells suppressed immune responses via the adenosine pathway by recruitment of myeloid-derived suppressor cells in colorectal cancer ( 39 ).…”

New Insights on CD8+ T Cells in Inflammatory Bowel Disease and Therapeutic Approaches

“…CD39 + CD8 + T cells, associated to a regulatory phenotype, are found within lamina propria under homeostatic conditions and their frequency is decreased in IBD patients compared to healthy controls ( 32 ). Similar results were reported by Huang et al in a pediatric IBD cohort.…”

“…Limited is the data reported on intraepithelial and lamina propria CD8 + T cells in health and IBD ( 95 ); however, few studies have ventured to provide such information. In homeostatic conditions, CD8 + T cell frequencies are slightly higher in lamina propria compared to PBMCs ( 32 ) reflecting the need of constant surveillance in the gut. Furthermore, intraepithelial and lamina propria compartments harbor similar CD8 + T cell subsets.…”

P2X7 is expressed on human innate‐like T lymphocytes and mediates susceptibility to ATP‐induced cell death

“…In the human T cell compartment, CD39 is mainly expressed on Tregs [61]. Peripheral blood Tγδ cells do not express CD39 [62], a further indication that P2X7-mediated cell death in these cells is plausible because they are not able to quickly degrade pericellular ATP. While ATP in the periphery is an immediate danger signal, commensal bacteria in the intestine constitutively release ATP [63,64], making the intestine an ATP-rich environment.…”