Inhibition of suppressor T-cell development following deoxyguanosine administration

Abstract

The expression of immunodeficiency in patients with specific purine enzyme defects indicates a crucial role of the purine salvage pathway in the acquisition and expression of normal immune function. One current hypothesis links the failure of normal lymphocyte development in these diseases to the accumulation of deoxynucleotide triphosphates. In our studies of human in vitro IgM responses, we observed that antigen-induced T-suppressor cell activity was abrogated in the presence of micromolar concentrations of deoxyguanosine (dGuo). In contrast, more than 1,000-fold higher resistance to dGuo was found for both noin-proliferative T-helper cell activity and the differentiation and proliferation of the precursor B lymphocytes for direct haemolytic plaque forming cells (PFC). To determine whether these observations could have in vivo relevance, we monitored the generation of murine T-suppressor cells, capable of abrogating a primary IgM response. It was found that dGuo (but not guanosine) selectively inhibited the in vivo development of T-suppressor cells.