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-alpha, IFN-gamma, and IL-6 action, ADA enhanced the differentiation of CD4(+)CD45RA(+)CD45RO(-) naive T cells toward CD4(+)CD25(+)CD45RO(+) Teffs and CD4(+)CD45RA(-)CD45RO(+) memory T cells. Furthermore, ADA potentiated generation of CD4(+)CD25(high)Foxp3(+) 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 immuno-logically compromised individuals. J. Leukoc. Biol. 89: 127-136; 2011.