Insights into Adenosine Deaminase Deficiency Provided by Murine Fetal Thymic Organ Culture with 2′-Deoxycoformycin

Abstract

Adenosine deaminase (ADA) deficiency as a cause of severe combined immunodeficiency (SCID) was first described twenty-five years ago.¹ One striking feature of this disease is that although the enzyme is missing in every cell in the body, the immune system is most severely affected. There is an almost complete absence of T cells and a variable decrease in the number of B cells. Gene therapy trials for ADA deficiency are well underway,^2,3 and ADA knockout mice have been generated by two groups^4,5 as a model to study this disease. Yet even after twenty-five years, the selective lymphotoxicity of ADA deficiency is still not understood. Understanding the mechanism of lymphotoxicity will not only teach us about the pathophysiology of this uncommon disease, but may lend insights into the therapy of this disease and the therapy of other lymphoid developmental defects. It may also give us clues to the design of new therapeutic options for more common lymphoid diseases such as malignancies, and will certainly teach us more about normal lymphocyte development.