CD150 CD4 T cells and CD150 regulatory T cells regulate hematopoietic stem cell quiescence via CD73.

Various extrinsic signals tightly control hematopoietic stem cell quiescence. Our recent study showed that hematopoietic stem cells are regulated by a special FoxP3 regulatory T-cell population with high expression of a hematopoietic stem cell marker, CD150. Extracellular adenosine generated via a cell-surface ectoenzyme CD39 on CD150 regulatory T cells maintained hematopoietic stem cell quiescence. It remains unclear how conventional T cells and the other cell-surface ectoenzyme, CD73, contribute to regulation of hematopoietic stem cells. This work shows that CD150 regulatory T cells as well as unique CD150 CD4 conventional T cells regulate hematopoietic stem cells via CD73. Global CD73 deletion increased the numbers of hematopoietic stem cells, cycling stem cell frequencies, and levels of reactive oxygen species in hematopoietic stem cells. antioxidant treatment inhibited the increase of hematopoietic stem cells in CD73 knockout mice, suggesting that CD73 maintains stem cell quiescence by preventing oxidative stress. High levels of CD73 expression were frequently found on CD150 regulatory T cells and CD150 FoxP3CD4 T cells within the bone marrow. Transfer of these CD150 regulatory T cells and CD150 CD4 conventional T cells abolished the increase of hematopoietic stem cells in CD73 knockout mice. In addition, the increase of stem cells in CD73 knockout mice was also inhibited by pharmacological activation of adenosine receptor 2A which is highly expressed by hematopoietic stem cells. Taken together, these results suggest that CD73 of CD150 regulatory T cells and CD150 CD4 conventional T cells protects hematopoietic stem cells from oxidative stress, maintaining stem cell quiescence via adenosine receptor 2A.