Abstract
CD73 is a membrane bound ectoenzyme, dephosphorylating adenosine mono- and di-phosphate to immunosuppressive adenosine. It is strongly expressed by CD4(+)CD25(+)Foxp3(+) regulatory T cells, but when analysing conventional CD4(+) T cells only 50% express CD73. When analysing these two clearly distinct (i.e., CD73(+) and CD73(-)) populations, we found that the naïve CD73(+)CD4(+) subset exerted superior proliferation over the CD73(-)CD4(+) cells, was more resistant to activation induced cells death (AICD) and was prone to develop into a "Th1-like" cell type, expressing the prototypic cytokines (IFN-γ, TNF-α) and specific transcription factors (i.e., Tbx21). Upon transfer into lymphopenic hosts, CD73(+)CD4(+) cells exhibited increased proliferation and survival, and accumulated in inflammatory tissues, developing a CD44(+)CD62L(-) effector memory phenotype. Therefore, we conclude that CD73 in naïve CD4(+) T cells functions as a promotor of survival and proliferation of T cells, as well as a marker for their further differentiation into effector T cells.