Inhibition by specific monosaccharides of interleukin 2-induced thymocyte proliferation.
When rat thymocytes are cultured for 3 days in serum-free medium and are stimulated to divide by interleukin 2 (IL 2), concanavalin A, or sodium periodate oxidation, addition to the medium of 10-25 mM D-ribose, 2-deoxy-D-ribose, or N-acetyl-D-galactosamine inhibits by 40% or more the incorporation of [3H]thymidine. D-ribose and lectin-free IL 2 generated from sodium periodate oxidation of rat spleen cells were used to study the characteristics of this inhibition and to test possible mechanisms of inhibition. Viability of thymocytes cultured with D-ribose is similar to that of cells cultured without this sugar. In order to be inhibitory, D-ribose has to be added to the cultures within the first 24 hr, and the inhibition can be prevented if the sugar is removed 18-24 hr after the start of culture. D-Ribose does not block the absorption of IL 2 by unstimulated rat thymocytes or by concanavalin A-generated thymic or splenic blast cells. When thymocytes are cultured with D-ribose for 24 hr, inactivated with mitomycin C, and then cultured for 3 days with fresh mitogenically stimulated cells, [3H]thymidine incorporation into the latter is not altered. This suggests that the sugar does not generate suppressor cells or suppressor supernates. D-Ribose does not appear to be a general metabolic inhibitor since [3H]leucine incorporation into thymocyte proteins and the release of [3H]leucine into medium after a 2-hr. [3H]leucine pulse are not altered by D-ribose. Trivial or artifactual effects (nonspecific cytotoxicity, changes in thymidine transport, or changes in isotonicity of the culture medium) cannot explain the inhibition. A hypothetical mechanism of inhibition is discussed.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A; D004261:DNA Replication / Q000187:drug effects; D006601:Hexoses / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009005:Monosaccharides / Q000494:pharmacology*; D010429:Pentoses / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012266:Ribose / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D006601:Hexoses; D007376:Interleukin-2; D009005:Monosaccharides; D010429:Pentoses; D003208:Concanavalin A; D012266:Ribose