The effect of purine and pyrimidine bases on splenic plaque-forming cells and cellular immunity.

The effects of a variety of purine and pyrimidine bases on splenic plaque-forming cells and cellular immunity in mice are presented. The antibody-forming plaque cells were measured in spleens of female C57/B1 mice by the Jerne plaque method using sheep red blood cells as the antigen. Bases were given on days 0 and 1 at doses varying from 2 to 200 mumoles per mouse and the antigen was given on day 0; the antibody response was measured on day 4. Cell-mediated immunity was measured by the survival of 1 cm2 skin allografts transplanted across an H-2 histocompatibility barrier in female mice from C57/B1 donors to Balb/c recipients. For the plaque assay, adenine given at 25 and 50 mumoles/mouse and adenosine at 100 mumoles/mouse, resulted in significant 7 to 14-fold immunosuppression. Adenosine at 25 and 50 mumoles/mouse and guanosine and hypoxanthine at 100 mumoles/mouse resulted in an approximate 2-fold immunoenhancement. 2'-Deoxyadenosine, inosine, guanine, 2'-deoxyguanosine and the pyrimidines cytosine, cytidine, 2'-deoxycytidine, 2'-deoxythymidine and uridine all given at 100 mumoles/mouse and orotic acid given at 25 mumoles/mouse had no significant effects on the plaque response; orotic acid at a dose of 50 mumoles/mouse was lethally toxic to mice. In the primary immune response adenine was immunosuppressive at day 4, but significantly immunoenhancing at days 7 and 11. In the secondary response, adenine was immunosuppressive up to day 3 of the IgG and IgM responses; however, immunoenhancement occurred at day 4 (IgM) and day 5 (IgG). In the cell-mediated immune response, adenine at doses of 25 and 50 mumoles/mouse resulted in a significant 40% increase in the survival of skin allografts across an H-2 histocompatibility barrier.