Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression

Human regulatory T cells (Treg) have been variously defined as CD4+CD25+, CD4+CD25high or CD4+CD25highFOXP3+ cells which are responsible for maintaining peripheral tolerance. Their isolation from human peripheral blood or tissues depends on the expression level of CD25(IL-2Rα) — a surface marker which is also expressed on activated effector helper T cells. CD39, a cell surface associated ectonucleotidase, can be used to purify Treg with strong suppressor functions. The CD4+CD39+ T cells catalyze cleavage of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), which is then further cleaved to adenosine. CD4+CD39+ T cells largely overlap with CD4+CD25highFOXP3+ but not CD4+CD25+ T cell subset, and mediate equally potent immune suppression. Thus, CD39 surface marker can be successfully used for routine isolation of functionally-active human Treg from the peripheral blood of healthy donors or patients with cancer for studies of their role in health and disease.