Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4⁺ T cells

By interacting with CD26 on the CD4⁺ T cell surface and with the AdoR A_2B on the DC surface, ADA triggers a costimulatory signal for human T cells. The aim of this study was to know whether ADA-mediated costimulation plays a role in the differentiation of T cells. The results show that irrespective of its enzymatic activity and dependent on TNF-α, IFN-γ, and IL-6 action, ADA enhanced the differentiation of CD4 ⁺CD45RA⁺CD45RO-naïve T cells toward CD4 ⁺CD25⁺CD45RO⁺ Teffs and CD4⁺CD45RA- CD45RO⁺ memory T cells. Furthermore, ADA potentiated generation of CD4⁺CD25^highFoxp3⁺ Tregs by a mechanism that seems to be mainly dependent on the enzymatic activity of ADA. Interestingly, an ADA-mediated increase on Teff, memory T cell, and Treg generation occurred, not only in cocultures from healthy individuals but also from HIV-infected patients. These data suggest that ADA is a relevant modulator of CD4⁺ T cell differentiation, even in cells from immunologically compromised individuals.