title: New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency.
abstract: There is growing interest in manipulating adenosine (Ado) signal transduction to control inflammation and autoimmunity. This concept probably originated with the discovery of severe combined immunodeficiency disease (SCID) in infants with inherited deficiency of adenosine deaminase (ADA). However, the basis for immunosuppression by Ado has not been well defined, and effects of 2'-deoxyadenosine (dAdo), which does not activate Ado receptors, have also been implicated in causing SCID. Here I discuss recent evidence that Ado, acting through its A2A receptor, interferes with NF-kappa B activation in antigen-receptor-stimulated B and T lymphocytes. I also assess the relative contributions of Ado and dAdo to the pathogenesis of ADA-deficient SCID.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. msh@biochem.duke.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hershfield
mesh_terms: D000241:Adenosine / Q000276:immunology; D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D003839:Deoxyadenosines / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D018047:Receptors, Purinergic P1 / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000209:etiology* / Q000276:immunology / Q000378:metabolism
chemical_list: D003839:Deoxyadenosines; D018047:Receptors, Purinergic P1; D000243:Adenosine Deaminase; D000241:Adenosine