STUDIES ON IMMUNOSUPPRESSION BY PURINE NUCLEOSIDE ANALOGUES .I. EFFECTS ON IMMUNE RESPONSE TO SHEEP RED BLOOD CELLS IN MICE

The time dependence of optimal immunosuppressive activity of several purine nucleoside analogs was studied using the Jerne et al. plaque assay technique to§ § N. K. Jerne and A. A. Nordin, Science, N. Y. 140, 405 (1963). N. K. Jerne, A. A. Nordin and C. Henry, in Cell-Bound Antibodies (Eds. B. Amos and H. Koprowski), p. 109. Wistar Institute Press, Philadelphia (1963). enumerate cells forming antibody to sheep red blood cells (SRBC) in mouse spleens. A single dose of drug was given before or at different times after a single dose of SRBC in order to determine the drug-sensitive phase of anti-SRBC antibody production in mouse spleens. α-2′-Deoxythioguanosine exhibited maximum activity during the proliferative phase of the immune response. β-D-Arabinofuranosyl-6-mercaptopurine showed activity only during a limited period of the proliferative phase. β-D-Ribosyl-6-methylthiopurine was active throughout the response. The periodate oxidation product of β-D-ribosyl-6-methylthiopurine (MMPR-OP) was active when given either before or after SRBC, as was the periodate oxidation product of inosine. 6-Methylthiopurine, one of the cleavage products of MMPR-OP was active only if given after SRBC. The results are discussed in terms of the effects of these drugs on cellular kinetics and metabolism. © 1969.