Mechanisms of Adenosine and 2’-Deoxyadenosine Inhibition of Immune Function in Mouse Lymphocytes

摘要: Adenosine (Ado) has been recognized as having an inhibitory influence on the immune system since 1970, when it was reported that this purine nucleoside inhibits mitogenic stimulation of human peripheral blood lymphocytes by phytohemagglutinin [1]. Widespread interest in possible modulatory role Ado sparked 1972 report Giblett and her colleagues [2] describing genetic deficiency enzyme deaminase (ADA) two children with severe combined immunodeficiency. This inherited disorder is characterized a marked reduction functional T B lymphocytes. With discovery additional immunodeficient patients lacking ADA, extensive research effort begun to elucidate biochemical mechanisms which ADA results rather selective demise system. From until 1978, widely assumed immunodeficiency disease from buildup high concentrations and/or adenine ribonucleotides ADA-deficient patients. Indeed, 1976 Mills et al. [3] plasma adenine, erythrocyte ATP, were elevated child. Accordingly, basis obtained number vitro model systems, several hypotheses introduced explain pathophysiology immunodeficiency, more prominent Ado-induced pyrimidine starvation, Ado-stimulated increases cAMP, Ado-mediated accumulation S-adenosylhomocysteine (AdoHcy) consequent inhibition methylation reactions (for reviews see [4–7]). Subsequently, 2′-deoxyadenosine (dAdo) urine dATP their erythrocytes further important observation dAdo toxic than proliferating lymphoid cells, emphasis studies concerning causal relationship between shifted away toward dAdo. The historical development interesting field subject recent [4–7].