CD73 Expression by CD4+ T Cells Marks Early Effector Memory T Cells.

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.