ENZYMATIC AND EXTRAENZYMATIC ROLE OF ECTO-ADENOSINE DEAMINASE IN LYMPHOCYTES

Adenosine deaminase (ADA, EC 3.5.4.4) is an enzyme of the purine metab olism which has been the object of considerable interest mainly becaus e the congenital defect causes severe combined immunodeficiency (SCID) . In the last 10 years, ADA, which was considered to be cytosolic, has been found on the cell surface of many cells and, therefore, it can b e considered an ecto-enzyme. There is recent evidence about a specific role of ecto-ADA, which is different from that of intracellular ADA. Apart from degrading extracellular adenosine (Ado) or 2'-deoxyadenosin e (dAdo), which are toxic for lymphocytes, ecto-ADA has an extraenzyma tic function via its interaction with CD26. ADA/CD26 interaction resul ts in co-stimulatory signals in T cells. This co-stimulation is blocke d by HIV-1, thus evidencing a role for ecto-ADA in the pathophysiology of AIDS. The fact that, besides CD26, ADA can interact with different cell-surface proteins opens new perspectives in the research for a ro le of ecto-ADA in the function of the immune system and in the interac tions that take place between different cells in the development of th e immune system. The most interesting aspect is the possible participa tion of the ecto-enzyme in cell-to-cell contacts during ontogenesis an d maturation of immunocompetent cells.