ADENOSINE DEAMINASE AND THYMOCYTE MATURATION

The congenital absence of adenosine deaminase in humans results in severe combined immunodeficiency. To clarity the process whereby thymocytes are destroyed in the absence of adenosine deaminase activity, we induced a parallel condition in mice through the injection of an inhibitor of adenosine deaminase, deoxycoformycin. We have observed that deoxycoformycin, in addition to maintaining high levels of dATP in thymocytes, blocks the progression of thymocyte differentiation at two points. As a result of the first block, the corlex is depleted of immature cortical thymocyles while CD4+ CD8+ thymocytes with functionally rearranged T-cell receptors survive. As a result of the second block, the CD4+ CD8− thymocytes are prevented from further differentiation lo mature CD4− CD8+ or CD4− CD8+ T lymphocytes and accumulate at the corticomedullar junction and in the medulla. These observations suggest that the maintenance of dNTP pools by adenosine deaminase is critical to at least two stages of thymocyte differentiation.