CD39 Is Expressed on Functional Effector and Tissue-resident Memory CD8+T Cells

The ecto-ATPase CD39 is expressed on exhausted CD8+ + T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ + T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ + short-lived effector cells, while it's ' s co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory T cell (TRM RM cell) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ + T cell differentiation. We also show that CD39 is expressed on human and murine T RM cells across several nonlymphoid tissues and melanoma, whereas CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ + T cells in chronic infection, CD39+ + T RM cells are fully functional when stimulated ex vivo with cognate Ag, further expanding the identity of CD39 beyond a T cell exhaustion marker. The Journal of Immunology, 2024, 213: 588-599.- 599.