Effect of purine nucleoside phosphorylase substrates on the mitogen-induced stimulation of murine T and B spleen cells.

The effect of culture with exogenous purine nucleoside phosphorylase substrates (especially deoxyguanosine) on the proliferation of mitogen-stimulated murine spleen cells was investigated. Con A-stimulated 3H-thymidine incorporation in unpurified and purified T cells was appreciably inhibited by culture in the presence of 100 microM deoxyguanosine. LPS-stimulated incorporation in unpurified and purified B cells was affected in a similar manner. Culture with guanosine inhibited incorporation in both mitogen-stimulated T and B cells to almost the same extent as deoxyguanosine. Inhibition of 3H-thymidine incorporation in T cells by deoxyguanosine was not modified by concomitant inclusion of deoxycytidine in the culture medium. In addition, deoxyguanosine had effects on T cell proliferative responses during the early phases of stimulation and even prior to stimulation with the mitogen. These results contrast with those reported for human lymphoid cells, where deoxyguanosine was much more potent that guanosine, and where only T cells were affected. They suggest that mechanisms other than the one involving inhibition of ribonucleotide reductase may also be important in the effects of deoxyguanosine on certain lymphoid cells.