Interleukin 2 liberation and absorption capacities of rat T lymphocytes in conditions of severe adenylic nucleotide pool depletion due to adenosine deaminase deficiency

In rat lymph node lymphocytes stimulated for 24 h by concanavalin A in the presence of 10−5M 2′-deoxycoformycin (a potent inhibitor of adenosine deaminase) and 10−5M 2′-deoxyadenosine the adenylic nucleotide pool was reduced by 55.5% without modification of either the adenylic energy charge or the ability of the cells to liberate interleukin 2. In the same conditions, the ability of rat spleen cells to bind exogenous interleukin 2 activity was not modified. The proliferative response to concanavalin A stimulation was completely inhibited after a 86-h culture period under adenosine deaminase deficiency conditions. It could not be restored by elimination of 2′-deoxyadenosine after a 20-h pretreatment, when adenylic nucleotide pool depletion was 72.4% whereas the interleukin 2 liberation ability was not suppressed. These results suggest that among the early consequences of adenosine deaminase deficiency conditions, which occur before S phase of the cell cycle, the depletion of adenylic nucleotide pool, rather than the impairment of interleukin 2 liberation and absorption capacities, may account for the inability of the lymphocytes to respond to mitogenic stimulation.